Part 1: Establishing Glycemic Control (The “A” of ABCS)


Hyperglycemia Is Linked to Abnormalities that Increase Cardiovascular Disease (CVD) Risk


Although multiple molecular mechanisms are implicated in the etiology of diabetes, the disease is characterized by an insulin insufficiency that, if untreated, promotes hyperglycemia and causes numerous microvascular and macrovascular complications. Most diabetes cases fall into one of two broad etiopathogenetic categories (Type 1 and Type 2; Table 1), with implications for management.2 However, some individuals may not be clearly classified as type 1 or type 2 at the time of diagnosis.


Table 1.  Etiopathogenetic Categories of Diabetes2


Percentage of Diabetes Cases




  • Absolute deficiency in insulin secretion
  • Autoimmune destruction of pancreatic β-cells



  • Insulin resistance
  • Pancreatic β-cell dysfunction
  • Progressive decline
  • No autoimmune destruction of β-cells

While type 1 diabetes treatment almost always necessitates insulin as a central component of management, T2DM may be managed without insulin (and without pharmacotherapy) in some cases. However, the hyperglycemia that characterizes T2DM rarely occurs in isolation. Insulin resistance is associated with hypertension and hyperlipidemia, factors that contribute to cardiometabolic risk.1 Moreover, most (but not all) patients with T2DM are obese (defined as a body mass index [BMI] > 30 kg/m2),7 which contributes to insulin resistance. Because of its spectrum of comorbidities, T2DM has been designated as a coronary heart disease (CHD) risk equivalent by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)-diabetes carries a risk for clinical CHD that is approximately equal to that of established CHD.8

Individuals who are diagnosed with T2DM often present with a constellation of atherogenic abnormalities that increases the risk for CHD and CVD.9-12 Although patients may present with different specific combinations of risk factors, the factors nonetheless often cluster in predisposed individuals. Numerous studies indicate that CVD risk rises as the number of abnormalities increases.10, 11, 13-16 Identification of one CHD risk factor should prompt the search for others and prompt the family physician, primary care physician, or other healthcare provider to begin proactive, aggressive treatment to reduce CVD risk. To this end, the ADA recommends that all individuals with diabetes be systematically assessed at least annually for CVD risk factors that include dyslipidemia, hypertension, smoking, a family history of premature coronary disease, chronic kidney disease, and the presence of albuminuria.17


Because T2DM is usually associated with a constellation of factors that are affected by diet, lifestyle, and environmental influences, family physicians, primary care physicians and other primary care /clinicians are uniquely positioned to identify risk factors and manage associated co-morbidities. T2DM can therefore be thought of as a paradigm for primary care, as it interfaces with the core attributes of family medicine: continuity of care, comprehensiveness, first contact, community, and family. The nature of T2DM requires that patients be followed over time to assure a reduction of risks. Moreover, it warrants a comprehensive treatment strategy, as several interventions will be required to optimize outcomes. Because T2DM often precedes or coincides with chronic conditions such as CHD and CVD, annual checkups and routine office visits offer the physician/clinician opportunities to identify individuals at risk. Early intervention by the family or primary care physician or other primary care clinicians complements and supports population-based strategies and communal approaches to reduce morbidity and mortality from CVD. Also, risk factors related to T2DM are influenced by familial genetic and environmental factors that may be recognized more easily in the family medicine/primary care setting.


Establishing Glycemic Control is Essential for Disease Management


Diabetes management aims to prevent microvascular (e.g., diabetic nephropathy, neuropathy, retinopathy) and macrovascular (e.g., coronary artery disease, peripheral arterial disease, stroke) complications and to improve quality of life.18 While no prospective randomized clinical trial in T2DM has been able to confirm the macrovascular benefits of glycemic control, epidemiologic studies, meta-analyses, and the ten-year follow-up of the United Kingdom Prospective Diabetes Study (UKPDS) suggest that macrovascular benefits are associated with good glycemic control.19-26 Moreover, the UKPDS demonstrated that tight control of glucose meaningfully impacts microvascular complications in patients with newly diagnosed T2DM.19, 20 These microvascular benefits persisted, and new macrovascular benefits were identified, at a ten-year follow-up in subjects who were treated intensively even if their glycemic control subsequently relaxed over time to that of the control arm of the trial.27 However, it is important to note that in outcomes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which compared the effect of intensive therapy (targeting an A1c level below 6.0%) versus standard therapy (targeting an A1c level between 7.0% and 7.9%) on cardiovascular events in patients with T2DM who had or were at risk for CVD, showed that intensive therapy for 3.5 years increased mortality yet did not significantly reduce major cardiovascular events.28 Moreover, the intensively treated cohort had higher incidence of hypoglycemia that required assistance and weight gain of more than 10 kg (P<0.001). This hypoglycemia may have contributed to the increased mortality in the intensive-therapy group, and physicians/clinicians would be wise to avoid hypoglycemia at whatever target glucose level is deemed appropriate for a given patient.  


To this end, the ADA29 and the International Diabetes Federation30 recommend an A1c goal of less than 7.0% for most adults diagnosed with diabetes, with the caveat that this goal may need to be more or less stringent depending on the individual’s comorbid medical conditions and risk of hypoglycemia.29 However, data from the National Health and Nutrition Examination Surveys (NHANES) from 1988-2010 indicate that 47% of adults with diabetes have an A1c level that exceeds 7.0%.31 Guidelines issued by the American Association of Clinical Endocrinologists suggest an A1c goal of < 6.5% for healthy individuals while emphasizing the need to individualize therapy.32


The ADA has issued glycemic recommendations for adults with diabetes (see callout box),29 noting that goals must be tailored to the individual patient and that providers must use clinical judgement when working with the patient to design an appropriate management plan. When suggesting an appropriate glycemic goal for a patient, the physician/clinician should consider various patient and disease factors, including risks associated with hypoglycemia or other adverse drug effects, disease duration, life expectancy, comorbidities, established vascular complications, patient attitude/expected treatment efforts, and the patient’s resources and support system.29


The risk of hypoglycemia among the elderly is of particular concern, as it may profoundly impact this population who may be particularly vulnerable to its consequences, either through limited capacity to recognize hypoglycemic symptoms or through clinical complications and comorbidities that can be exacerbated by hypoglycemia. Elderly patients who experience hypoglycemic episodes may be physically frail and thus risk potentially serious physical injury from falls or other accidents. A well-tailored diabetes intervention must minimize hypoglycemic episodes, a facet of treatment that should be emphasized for the elderly patient. In its 2018 Standards of Medical Care in Diabetes, the ADA provides a framework for considering treatment goals for glycemia and other CVD risk factors in older adults with diabetes.33 


2018 ADA Glycemic Recommendations for Non-Pregnant Adults with Diabetes:29


A1c:                                                   < 7.0*

Preprandial capillary PG:                80-130 mg/dL*

Peak postprandial capillary PG§:      <180 mg/dL*


*Individualize based on age/life expectancy, duration of diabetes, comorbid conditions, known CVD or advanced microvascular complications, hypoglycemia unawareness, and patient considerations. More or less stringent goals may be appropriate for some patients.


§Postprandial glucose may be targeted if A1c goals are not met despite reaching preprandial glucose goals. Postprandial glucose measurements should be made 1–2 hours after the beginning of the meal, when levels generally peak in patients with diabetes.


Components of an Effective Intervention for Patients with T2DM


Diabetes is a chronic condition, and its management extends beyond glucose control. Diabetes has been associated with numerous comorbidities, prompting the ADA to include a section in its 2018 Standards of Medical Care in Diabetes to address the assessment of many comorbidities, including cancer, cognitive impairment, fatty liver disease, HIV infection, pancreatitis, and others.7 Regardless of patient-specific comorbidities and CVD risk factors, diabetes management requires a holistic approach that consists of three overlapping components: 1) diabetes self-management education and support, 2) medical nutrition therapy (MNT; the process of establishing a tailored nutrition prescription), and 3) pharmacotherapy (for glycemic control and/or complications). These topics are discussed in detail below. To achieve optimal health outcomes and health-related quality of life, the ADA recommends that the physician/clinician be attuned to the needs of the patient during conversations, eliciting patient preferences and beliefs, assessing literacy, numeracy and potential barriers to care, and listening actively for cues that will aid in management.7


Diabetes Self-Management Education (DSME) and Support (DSMS). DSME and DSMS are interactive, ongoing educational programs, usually hospital- or community-based, that connect patients with diabetes with a diabetes educator(s), with a goal of helping patients make informed self-management decisions.34 The ADA stresses that DSME and DSMS should be patient-centered, respectful, and responsive to individual patient preferences, needs, and values and should be used to help guide clinical decisions.34 Each patient should receive an individualized assessment of his/her condition, identification of personal self-management goals, an educational plan and interventions, and periodic reassessments of progress and goals. In this process, the physician/clinician should consider the patient’s attitude and beliefs about diabetes when tailoring a treatment strategy. DSME has been associated with numerous beneficial outcomes, including improved self-care behaviors, lowered A1c, reductions in self-reported weight, healthy coping strategies, reduced cost, and improved quality of life.34 Current ADA criteria for a DSME curriculum with successful learning outcomes include the following:35


  • Describing the diabetes disease process and treatment options
  • Incorporating nutritional management and physical activity into lifestyle
  • Using medications safely and for maximum therapeutic effectiveness
  • Monitoring blood glucose and other parameters and interpreting/using the results for self-management decision-making
  • Preventing, detecting, and treating acute and chronic complications
  • Developing personal strategies to address psychosocial issues/concerns and to promote health and behavior change.


DSME and DSMS may be reimbursed through the Centers for Medicare and Medicaid Services (CMS) and many private payers. However, programs must be recognized or accredited by a CMS-designated national accreditation organization such as the ADA or American Association of Diabetes Educators (AADE) to be eligible for reimbursement. As such, DSME/DSMS programs have traditionally existed as outpatient services at hospitals or health facilities, although they are becoming increasingly incorporated into office practices and patient-centered medical homes (PCMHs). Practices that will refer patients for DSME /DSMS should manage this process as they would any other referral. The ADA, AADE, and the Academy of Nutrition and Dietetics recommend that DSME/DSMS be assessed and provided at diagnosis, during annual assessments of educational, nutritional, and emotional needs, when new complicating factors influence self-management, and during transitions in care.36


Nearly all states have received CDC funding to improve the number and quality DSME and DSMS programs. Practices can find programs through the American Association of Diabetes Educators at


DSME and/or DSMS are additive therapies and not meant to be used in a singular instance or to replace any diabetes self-management education that is managed within the practice. In fact, diabetes self-management represents a partnership between the patient and provider. In 2015, the ADA and the European Association for the Study of Diabetes (EASD) released a joint position statement advocating for patient involvement in decision making with regard to T2DM management,37 and the ADA and the IDF continue to advocate for the role of the patient in the management of T2DM.7, 30 The ADA/EASD recommendations support a shared decision-making approach that applies to primary care practices and those practices that incorporate the PCMH.[1] For the patient, effectively managing T2DM requires collaboration, a personalized management plan, self-management education, adherence to treatment, and appropriate follow-up and monitoring. Successful approaches aimed at improving self-management are planned and feature defined targets and established goal-setting. Several approaches, including diabetes “mini-clinics,” structured behavioral interventions, multidisciplinary disease programs, and methods to improve organization and delivery of patient education, have been explored in primary care settings to improve care for patients with diabetes.38, 39 Patients with diabetes who have been managed through various PCMH programs have demonstrated improvements in disease-related factors such as A1c, blood pressure, and low-density lipoprotein (LDL) cholesterol, with concomitant reductions in medical costs and inpatient admissions.39 


Persons with diabetes can benefit from monitoring their blood glucose to prevent hypo- and hyperglycemia. Self-monitoring of blood glucose (SMBG) is a central component of diabetes management, because it enables patients to evaluate their individual response to therapy and assess whether glycemic targets are being achieved.29 Integrating SMBG results into diabetes management can help to guide medical nutrition therapy and physical activity, prevent hypoglycemia, and adjust medications accordingly. Monitoring can help to show the effects of food choices, exercise, medications, and stress on blood sugar readings, and blood glucose should be monitored more often when adding or modifying a therapeutic regimen. Patients should be educated on ways to recognize, prevent, and treat hypoglycemia and to understand when continuous glucose monitoring may be beneficial.


Medical Nutrition Therapy (MNT). MNT, an essential component of any DSME program, is the process of establishing a tailored nutrition prescription (preferably overseen by a registered dietitian or Certified Diabetes Educator (CDE) who is knowledgeable in providing diabetes MNT) based on an individual’s medical, lifestyle, and personal factors.40 Key components of MNT include caloric intake/portion control, weight loss and management through diet and physical activity, a consistent daily carbohydrate intake, balanced nutritional content, and effective meal timing. The process of MNT involves selecting an appropriate meal-planning approach and educational materials that consider a person’s clinical or nutritional goals, ability or willingness to learn, motivation to change eating or behavioral habits, activity level, and lifestyle. MNT aims to achieve several goals (see callout box),34 and compliance is critical for attaining glycemic control.


MNT promotes modest weight loss through a tailored program of lifestyle change.35 Structured programs that include education, reduced intake of calories and fats, regular physical activity, and regular contact between the individual and the healthcare team can facilitate long-term moderate weight loss, thereby reducing hyperglycemia, dyslipidemia, and hypertension. Monitoring carbohydrate intake is a key strategy to achieving glycemic control. To achieve and maintain a healthy weight, the ADA recommends reducing  saturated fat intake below 7% of the total caloric intake, minimizing intake of trans fats, increasing fiber, and avoiding high-protein diets.40 Blood glucose monitoring provides the practical information to assess changes in MNT.


ADA Goals of MNT for Adults with Diabetes:34


  • Promote and support healthful eating patterns, emphasizing various nutrient-dense foods in appropriate portion sizes to improve overall health and specifically to attain individualized glycemic, blood pressure, and lipid goals, achieve/maintain body weight goals, and delay/prevent complications from diabetes.
  • Address individual nutrition needs based on personal and cultural preferences (e.g., the meaning and impact of food on family life), health literacy and numeracy, access to healthful foods, willingness and ability to make behavioral choices, and barriers to change.
  • Maintain the pleasure of eating by providing non-judgmental messages about food choices.
  • Provide practical tools for developing healthy eating patterns to the individual with diabetes rather than focusing on individual macronutrients, micronutrients, or single foods.


Pharmacotherapy. For disease management, pharmacotherapy may be indicated in addition to a lifestyle regimen that promotes cardiovascular health.32, 41 Options include oral and parenteral antihyperglycemic agents. Approved oral agents target various defects associated with T2DM, including insulin resistance, decreased insulin secretion, increased hepatic glucose output, and increased glucose uptake by the kidneys. When used as monotherapy, most antihyperglycemic medications decrease the A1c level by approximately 1%, and each new class of non-insulin agents that is added to initial therapy will lower A1c by approximately an additional 1%.42 Oral agents are indicated and commonly used in combination therapy regimens. Evidence-based strategies to incorporate pharmacotherapy into T2DM management have been generated by several professional organizations, including the ADA41 and the American Association of Clinical Endocrinologists (AACE).32, 43


Initiating Pharmacotherapy. The ADA recommends that metformin be used as the initial pharmacologic agent for treating T2DM, beginning at the time of diagnosis, assuming that it is tolerated and not otherwise contraindicated (Figure 1).41 Metformin is an inexpensive and extensively-studied agent that has been proven safe and effective with long-term follow-up periods of up to a decade.27, 44 Cardiovascular mortality is lower for metformin than for the sulfonylureas, another class of oral antihyperglycemic agents that is commonly used as first-line therapy.44 However, long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and the ADA recommends considering periodic measurement of vitamin B12 levels in metformin-treated patients, especially those with anemia or peripheral neuropathy.41 Historically, metformin has not been recommended for individuals with impaired renal function, but meta-analyses have shown its safety in persons with an estimated glomerular filtration rate (eGFR) as low as 30 mL/min/1.73 m2,42 prompting the US Food and Drug Administration (FDA) to revise its product labeling in April 2016 to indicate metformin use in individuals with eGFR > 30 mL/min/1.73 m2.45 As part of this communication, the US FDA also recommends that eGFR be used as the measure of kidney function when determining suitability for metformin, as it provides a better estimate of kidney function in individuals with kidney disease than does blood creatinine concentration, a measurement based on a single laboratory parameter.


Figure 1. ADA general recommendations for antihyperglycemic therapy in T2DM.41


Continuing when a Single Agent is No Longer Sufficient. As noted in Figure 1, antihyperglycemic agents are often used in combination, and the physician/clinician should expect to modify initial monotherapy regimens as the disease progresses. To this end, the ADA recommends that a second agent be added to non-insulin monotherapy if the maximum tolerated dose of the initial agent fails to achieve or maintain the A1c target after three months.41 For patients with atherosclerotic CVD (ASCVD), the second agent should be proven to reduce major adverse CV events and/or CV mortality (see discussions below). The ADA also recommends that a patient initiate insulin if triple therapy fails to control glucose levels.


Initiating Insulin. The ADA and EASD recommend basal insulin as an option in combination with metformin when dual therapy is necessary and with metformin plus a thiazolidinedione (TZD), dipeptidyl peptidase 4 (DPP-4) inhibitor, sodium glucose cotransporter 2 (SGLT2) inhibitor, or glucagon-like peptide-1 (GLP-1) agonist when triple therapy is warranted to achieve glycemic goals (Figure 1).37, 41 The ADA recommends combination injectable therapy (e.g., basal insulin plus mealtime insulin or a GLP-1 agonist) as initial therapy in individuals whose blood glucose is > 300 mg/dL or A1c > 10% or if the patient has signs of hyperglycemia, such as polyuria or polydipsia. This recommendation is included in the ADA’s 2018 Standards of Medical Care in Diabetes.41


The ADA notes that basal insulin represents the most convenient starting point for insulin-naïve patients, beginning at 10 U or 0.1-0.2 U/kg daily, depending on the degree of hypoglycemia.41 While the titration must be individualized, one suggested approach is to have the patient check his/her blood glucose daily and adjust the insulin dose on a weekly basis as needed. As the fasting plasma glucose value approaches target, the titration increment (e.g., the increase in insulin units/day) is reduced.46 If basal insulin has been titrated to an acceptable fasting blood glucose level but A1c remains above target, ADA recommends considering combination injectable therapy (e.g., basal insulin plus a GLP-1 receptor agonist or a rapid-acting insulin) to cover glycemic variations induced by meals. The strategy to administer basal insulin plus injections of rapid-acting insulin before meals is often characterized as a “basal-bolus” regimen, and this approach provides greater flexibility than premixed insulins. Figure 2 provides ADA recommendations for initiating and advancing insulin regimens, with dose titration based on blood glucose levels. Although non-insulin agents may be continued with basal insulin therapy, sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists are often discontinued when the insulin regimen becomes more complex and costly.


Figure 2. ADA schematic for combination injectable therapy for T2DM.41




Table 2 summarizes ADA recommendations for pharmacologic therapy for T2DM, along with grades of supporting evidence.


Table 2. ADA Recommendations for Pharmacologic Therapy for T2DM41


Level of Evidence*

Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacological agent for T2DM.


In patients with newly-diagnosed T2DM and symptomatic and/or with blood glucose levels > 300 mg/dL or A1c > 10%, consider initiating insulin therapy (with or without additional agents).


Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy.


Consider initiating dual therapy in patients with newly-diagnosed T2DM who have A1c > 9%.


In patients without ASCVD, if monotherapy or dual therapy does not achieve or maintain the A1c goal over three months, add an additional antihyperglycemic agent based on drug-specific and patient factors.


In patients with T2DM and established ASCVD, antihyperglycemic therapy should begin with lifestyle management and metformin and subsequently incorporate an agent proven to reduce major adverse CV events and CV mortality (currently empagliflozin and liraglutide), after considering drug-specific and patient factors.


In patients with T2DM and established ASCVD, after lifestyle management and metformin, canagliflozin may be considered to reduce major adverse CV events, based on drug-specific and patient factors.


Continuous reevaluation of the medication regimen and adjustment as needed to incorporate patient factors and regimen complexity is recommended.


A patient-centered approach should be used to guide choice of pharmacologic agents. Considerations include efficacy, hypoglycemia risk, impact on weight, history of ASCVD, potential side effects, renal effects, delivery method, cost, and patient preferences.


For patients with T2DM who are not achieving glycemic goals, drug intensification, including consideration of insulin therapy, should not be delayed.


Metformin should be continued when used in combination with other agents, including insulin, if not contraindicated and if tolerated.


*ADA evidence grading system for these recommendations:47

Level A: Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered (including evidence from a well-conducted multicenter trial or evidence from a meta-analysis that incorporated quality ratings in the analysis), compelling non-experimental evidence (e.g., the “all or none” rule developed by the Centre for Evidence-Based Medicine at the University of Oxford), supportive evidence from well-conducted randomized controlled trials that are adequately powered (including evidence from a well-conducted trial at one or more institutions or evidence from a meta-analysis that incorporated quality ratings in the analysis).

Level B: Supportive evidence from well-conducted cohort studies (e.g., evidence from a well-conducted prospective cohort study or registry or evidence from a well-conducted meta-analysis of cohort studies) or from a well-conducted case-control study.

Level C: Supportive evidence from poorly-controlled or uncontrolled studies (e.g., randomized clinical trials with one or more major or three or more minor methodologic flaws that could invalidate the results, observational studies with high potential for bias, case series/reports) or conflicting evidence with the weight of evidence that supports the recommendation.

Level E: Expert consensus or clinical experience.


Considerations in the Context of Cardiovascular Health. All classes of antihyperglycemic agents are associated with side effects, some of which may be related to cardiovascular health. In particular, thiazolidinediones (TZDs) may cause edema and have been reported to be significantly associated with a higher risk of heart failure in adults with or at a high risk for T2DM.48, 49


 Physicians/clinicians are advised to use clinical judgement when considering TZDs as part of a management plan for patients with T2DM, especially in the setting of preexistent CHF. To this end, the ADA states that TZD use should be avoided in patients with symptomatic heart failure.17


However, cardiovascular outcome data from three large, randomized, controlled trials have shown statistically significant reductions in CV events with use of the SGLT2 inhibitors, empagliflozin50 and canagliflozin,51 and for the GLP-1 receptor, liraglutide.52 In the studies, these agents were often used in combination with metformin. The majority of patients in these trials had ASCVD, leading the ADA to develop recommendations (see Table 2) that specifically reference these agents in the context of treating patients with type 2 diabetes and ASCVD. Results from the three trials are briefly reviewed below.


Data from the placebo-controlled EMPA-REG OUTCOME Trial of 7,020 individuals with T2DM at high risk for cardiovascular events who received empagliflozin (median observation time: 3.1 years) indicate that those who received the drug in addition to standard care had a lower rate of the primary composite cardiovascular outcome and of death from any cause, relative to placebo.50 Based on these data, the US FDA added a new indication for empagliflozin in December 2016 to reduce the risk of cardiovascular death in adult patients with T2DM and CVD.53 Another trial, the Canagliflozin Cardiovascular Assessment Study (CANVAS; n=10,142), compared canagliflozin with placebo in patients with type 2 diabetes and high risk for ASCVD for a mean follow up of 188.2 weeks.51 Subjects who received canagliflozin had a lower rate of the primary outcome, defined as a composite of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. However, canagliflozin was associated with an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75), primarily at the level of the toe or metatarsal. Although renal outcomes were not statistically significant in the CANVAS trial, possible benefits of canagliflozin with respect to the progression of albuminuria and the composite outcome of a sustained 40% reduction in eGFR, the need for renal-replacement therapy, or death from renal causes are being investigated in a follow-up study (CANVAS-R; n=5,812).54  


Another recent trial, the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results: A Long-term Evaluation (LEADER), evaluated the cardiovascular effect of the GLP-1 receptor agonist when added to standard of care in 9,340 individuals with T2DM who are at high cardiovascular risk.52 Over a median follow up of 3.8 years, the primary composite outcome (first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke) occurred in 13.0% of participants in the treatment group, compared to 14.9% in the placebo group. A similarly-designed trial (SUSTAIN-6; n=3,297) using semaglutide administered once weekly for 104 weeks to patients with T2DM who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among subjects who received semaglutide than among those who received placebo.55 It remains to be seen whether other GLP-1 agonists will have the same effect in high-risk patients or whether any of these agents will have similar effects in lower-risk patients.   


It is important to note that in outcomes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which compared the effect of intensive therapy (targeting an A1c level below 6.0%) versus standard therapy (targeting an A1c level between 7.0% and 7.9%) on cardiovascular events in persons with long-standing T2DM who had or were at high risk for CVD, showed that intensive therapy for 3.5 years increased mortality yet did not significantly reduce major cardiovascular events.28 The increased mortality occurred primarily in patients randomized to the intensive therapy arm, who continued to have elevated A1c despite every effort being made to establish glycemic control. Importantly, the intensively-treated cohort had a higher incidence of hypoglycemia that required assistance and experienced weight gain of more than 10 kg (P<0.001). This hypoglycemia may have contributed to the increased mortality in the intensive-therapy group, and the physician/clinician would be wise to avoid hypoglycemia at whatever target glucose level is deemed appropriate for a given patient.    


Considerations for a T2DM Management Plan


Because cardiometabolic risk factors tend to cluster, diabetes care extends beyond tight glycemic control. Managing T2DM should generally incorporate four areas:34


  1. Lifestyle interventions for overweight and obese individuals that are geared toward an initial loss of 5-10% of baseline body weight through the combination of 150 or more minutes of physical activity per week (if the patient is capable) and a low-fat, ADA-appropriate reduced-calorie diet.
  2. Management of cardiovascular risk factors (e.g., hypertension, dyslipidemia, and microalbuminuria) using aspirin, statins, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers.
  3. Normalization of blood glucose levels, as monitored using A1c level.
  4. Patient preferences and individualized care goals (e.g., smoking cessation).


Combined Moderate Weight Loss and Physical Activity Lowers Diabetes Risk. Results from the Diabetes Prevention Program (DPP) indicate that loss of 5-10% of body weight through lifestyle modification decreases progression to T2DM regardless of age, sex, or ethnicity.56-58 In the DPP study, lifestyle therapy reduced the risk of developing T2DM among subjects with impaired glucose tolerance by 58% relative to placebo, nearly doubling that achieved by pharmacotherapy with metformin. Successful lifestyle therapy involves a low-fat/ADA-appropriate reduced-calorie diet, physical activity, and frequent intervention with dietitians or lifestyle coaches. In an extensive review of the literature, the National Heart, Lung, and Blood Institute (NHLBI)59 concluded that the strength of evidence was high to support the following statements:


  • In overweight and obese adults at risk for T2DM, average weight losses of 2.5-5.5 kg (5.8 – 12.2 pounds) at 2 or more years, achieved with lifestyle treatment (with or without orlistat), reduces the risk for developing T2DM by 30-60%.
  • In overweight and obese adults with T2DM, 2-5 % weight loss achieved with 1 to 4 years of lifestyle treatment (with or without orlistat) results in modest reductions in fasting plasma glucose concentrations and lowering of A1c by 0.2-0.3%.
  • In overweight and obese adults with T2DM, those who achieve greater weight loss at 1 year with lifestyle therapy (with or without orlistat) have greater improvements in A1c. Weight loss of 5-10% is associated with A1c reductions of 0.6-1.0% and reduced need for diabetes medications.
  • In overweight or obese adults with or without elevated CVD risk, there is a dose-response relationship between the amount of weight loss achieved by lifestyle intervention and the improvement in lipid profile.


Achieving a Balanced Diet. Weight loss occurs when the amount of expended energy exceeds the caloric intake, while weight maintenance reflects a balance between intake and expenditure. For controlled weight loss, a healthy diet must create a daily deficit in energy (calories). Because each pound of adipose tissue stores approximately 3,500 calories,60 a tailored diet that targets a deficit of 500 to 1,000 cal/day will promote the loss of 1-2 lbs/week.59 Weight loss that exceeds this rate results in loss of water and muscle mass, thereby increasing health risks and encouraging weight regain.

Although caloric balance is the major determinant of weight loss, a healthy strategy requires more than simply cutting calories--nutritional balance and weight management are complementary goals to weight loss. Effective management represents a long-term lifestyle change through the adjustment of daily eating habits. Thus, any diet should be planned to achieve a gradual but progressive weight loss, and dietary adjustments should enfold into an overall lifestyle regimen that includes physical activity (see below for details).

A low-calorie diet, with consideration given to the patient's food preferences, is the first step. According to evidence-based studies, the USDA reports that, in the absence of physical activity, any diet containing approximately 1,400 to 1,500 cal/day will result in weight loss, regardless of macronutrient composition.61 In addition, reducing the portion of fat intake in the diet can promote a small decrease in body weight, BMI, and waist circumference.62 However, the number of kcal/day necessary for weight loss or maintenance depends on the individual patient's usual caloric intake, and any caloric regimen must be tailored to the individual patient. A resource for patients to help design and track a healthy personal eating/activity plan is available at the US Department of Agriculture’s “MyPlate/MiPlato” website ( A detailed review of the evidence to support various dietary strategies is available from the NHLBI,59 and the ADA provides evidence-based MNT recommendations on macronutrient distribution,34 with the caveat that there is no universal ideal macronutrient distribution—eating plans must be individualized to achieve optimal results. For further consultation, a registered dietitian can be located through the Academy of Nutrition and Dietetics (


Simple, Healthy Dietary Take-Home Concepts for the Patient:

  • Drink a protein shake for breakfast rather than sodas or juice
  • Plan and prepare meals at home rather than ordering take-out
  • Pay attention to portion and serving sizes
  • Select high-fiber foods when possible
  • Choose broiled, boiled, or steamed food instead of fried
  • Consider calorie-controlled meals as one component of an ADA-appropriate diet


Promoting Physical Activity. A recent meta-analysis of 47 randomized, controlled clinical trials indicates that structured exercise training (aerobic, resistance, or both) is associated with reduced A1c concentration in persons with T2DM.63 This reduction was greater for persons who exercised at least 150 minutes per week. Structured exercise confers numerous health benefits (e.g., cardiovascular fitness, muscle strength, improved insulin sensitivity, increased mobility in overweight persons) for both the general population and individuals with T2DM.64 The ADA recommends that most adults with T2DM engage in least 150 min/week of moderately to vigorously intense physical activity, spread over at least three days per week with no more than two consecutive days without activity (Evidence Category: B).34 The ADA notes that shorter durations (e.g., a minimum of 75 minutes/week) of vigorous-intensity or interval training may be sufficient for younger and more physically fit individuals. The ADA also recommends that adults with T2DM engage in 2-3 sessions/week of resistance exercise on nonconsecutive days (Evidence Category: B).34

The ADA has consistently offered the aforementioned recommendations for physical activity, with slight adjustments, for the previous few

years. However, beginning with its 2017 Standards of Medical Care in Diabetes, the Association addressed an emerging body of literature that links a sedentary lifestyle with mortality and risk of chronic disease. Several studies in European cohorts have suggested that physical activity derived from occupation or commuting to work is associated with reduced risk of heart failure,65 reduction in total and CVD mortality among individuals with T2DM,66 and reduction in cardiovascular mortality in adults with hypertension.67 These studies support the principle that activity, no matter how it is derived, bestows multiple health benefits. However, recent studies have begun to assess the long-term negative impact of inactivity or the benefits of briefly interrupting sedentary periods. For example, one long-term study of more than 17,000 individuals aged 18-90 years (average follow up of 12.0 years) indicates a “dose-response” association between time spent sitting and mortality from all causes and from CVD, independent of the physical activity obtained from leisure-time endeavors.68 In a small study among 24 inactive, overweight/obese adults with T2DM, non-control subjects were required to interrupt sitting every 30 minutes with at least three minutes of light walking or simple resistance activities (e.g., knee raises, half-squats, calf raises).69 Standardized meals were consumed by all participants, and researchers measured postprandial cardiometabolic risk factors. Interrupting prolonged sitting, even with brief bouts of movement, attenuated postprandial glucose, insulin, C-peptide, and triglyceride responses in those patients with T2DM. Based on these and other emerging data, the ADA now recommends that all adults, particularly those with T2DM, decrease the amount of time spent in sedentary behavior (Evidence Category: B) and that prolonged sitting should be interrupted every 30 minutes for blood glucose benefits, particularly in adults with T2DM (Evidence Category: C).34


When helping patients to establish a physical activity regimen, the physician/clinician should stress that activity does not necessarily equatewith traditional exercise and may include walking, sports, and common chores (e.g., gardening, waxing a car, pushing a stroller, raking leaves). A useful physical activity goal is 30 minutes or more of moderate exercise each day. This activity is cumulative—to attain benefits, an individual need not complete the activity in a single, consecutive period. Thus, a person could walk 30 minutes once daily or split this level of activity in a manner that suits daily schedules (e.g., 10 minutes before work, 10 minutes at lunch or break, and 10 minutes after dinner). To encourage activity, the provider can ask a patient to wear a pedometer for a week and record the number of steps taken each day, with a target goal of achieving 10,000 steps per day. For patients with multiple CVD risk factors, physical activity should be initiated slowly and increased gradually, and any patient who is starting an activity program should be evaluated for cardiovascular fitness prior to commencement.


Persons with diabetes should complete 30 minutes or more of moderate exercise each day, which can be carried out in one session or a series of brief sessions.


As with dietary intervention, a physical activity plan should be tailored to the individual, with the understanding that each patient will progress through an activity regimen at an individual rate. Table 3 provides suggestions to increase physical activity during daily routines.


Table 3. Physical Activity Suggestions During Daily Routines
  • Use stairs instead of the elevator
  • Park farther away from work or shopping
  • Walk at lunch time
  • Exit public transportation one stop before the usual one
  • Use a pedometer to count steps
  • Limit television viewing to 1 hour per day
  • When watching television, stand or walk during commercial breaks


According to data from the National Weight Control Registry, most persons who lost significant weight and maintained the loss for more than one year report engaging in high levels of physical activity (~1 hour/day), eating a low-calorie, low-fat diet, eating breakfast regularly, self-monitoring their weight, and maintaining a consistent eating pattern across weekdays and weekends.70 Although any intervention must be tailored to the patient’s needs, all strategies to lose weight safely incorporate themes of variety, proportionality, moderation, and physical activity.


Losing 5-10% of body weight through lifestyle modification decreases progression to T2DM, regardless of a person’s age, sex, or ethnicity.


Behavioral Modifications Require Active Patient Participation. Successful behavioral modification requires that the patient take responsibility for his/her actions by setting specific health/lifestyle goals and achieving them in large part through self-management. Numerous patient factors, including motivation level, support systems, time, stress level, and attitude toward physical activity can influence adherence to a given regimen. As such, the provider must assess the patient’s readiness to undertake a lifestyle regimen (see section on “Assessing Stages of Change” for discussion).


Adherence relies on accountability; therefore, patients must be encouraged to use all possible tools to maintain momentum. When encouraging patients, the physician or other healthcare provider should recognize the emotional effect of living with diabetes—stress can affect insulin and blood glucose levels and undermine healthy eating, activity and self-monitoring schedules, and adherence to medications. A useful goal-setting starting point is to have the patient describe a typical day in his or her life that recounts eating habits, physical activity, and time considerations. The following strategies may be useful when working with a patient to develop a regimen with realistic goals:


  • Maintain a daily diet/exercise diary (which can be reviewed at follow-up visits)
  • Identify (and, where possible, avoid) situations that may compromise goals and plans
  • Recognize success at follow-up visits
  • Identify a social network and support system (e.g., family and friends, group-visit intervention sessions, established organizations such as Weight Watchers®)
  • Set realistic goals and a specific plan developed with patient input
  • Establish a self-management action plan based on what the patient feels that he/she can achieve with high confidence
Numerous self-management goal-setting forms and tools for patients and providers (in English and Spanish) are available from the Robert Wood Johnson Foundation’s Diabetes Initiative at:


In addition, numerous smartphone apps can assist with tracking calories and exercise, including GoMeals®, CalorieKingTM, and MyFitnessPalTM.*


*NJAFP does not endorse these apps, but simply offers them as a resource.


For those patients who are undertaking lifestyle transitions but do not wish to join established social support groups, the family physician or other healthcare provider should schedule frequent follow-up visits to assess progress. 


Communication and Team Efforts Enhance Success. Managing long-term complications of T2DM requires continuing care and education; the patient and the entire healthcare team must communicate in an interactive, collaborative, and ongoing process. Care should be administered by a multi-disciplinary, primary care physician-facilitated team that may include a registered dietitian, a behaviorist, an exercise physiologist, an ophthalmologist, a pharmacist, a specialist physician, a podiatrist, a diabetes educator, and other healthcare professionals. It is imperative that the patient interact frequently and regularly with team members. Certain healthcare professionals have special expertise in diabetes education. Assistance in locating certified diabetes educators (CDEs) and creating a team is available from the American Association of Diabetes Educators at


A supportive network for the patient is a key facet of a successful intervention. The DPP study, which featured 16 sessions with a registered dietitian within the first six months of treatment and at least one session every other month for the subsequent 30 months, demonstrated the effectiveness of an intensive, face-to-face intervention in helping patients manage weight over a period of four years.56 This intervention helped to promote an average 7% loss in body weight over the first year, 4% of which was maintained after four years.71


An Informed Patient is an Empowered Patient. Productive interactions between an informed, activated patient (and his/her family and caregivers) and a prepared health care team constitute a continuous healing relationship. An informed, activated patient understands the T2DM disease process and realizes his/her role in daily management. To optimize health outcomes and promote a high quality of life, the health care team must work to foster the patient’s sense of control and responsibility. A prepared practice team will have relevant information, decision support, staff, equipment, and time required to deliver evidence-based clinical management and self-management support at the time of the patient visit.


Motivational Interviewing and the “5 A”s of Intervention. Patients who are embarking upon a regimen of lifestyle/behavioral changes will arrive at the office in various stages of readiness. Physicians/clinicians are thus encouraged to practice motivational interviewing, an approach based on five general principles:72


  1. Expressing empathy through reflective listening
  2. Developing a discrepancy between clients' goals or values and their current behavior
  3. Avoiding argument and direct confrontation
  4. Adjusting to client resistance rather than opposing it directly
  5. Supporting self-efficacy and optimism


The provider can use the office model of the “5 A’s” as an approach when designing an appropriate intervention. This model, which is commonly associated with interventions for smoking cessation, can be applied to any process of healthy behavioral/lifestyle change, including those that enhance glycemic control.73 The “5 A’s” are ask, advise, agree and assess, assist, and arrange. The appropriate action by the physician or member of the healthcare team for each step is provided in Table 4. These strategies are not time-consuming and can be integrated smoothly into routine office visits and group-based diabetes interventions.


Table 4. The “5 A”s: An Intervention Strategy to Help Patients Achieve Behavioral Changes73


Physician or Healthcare Team Action


Identify and document lifestyle habits and behaviors (including alcohol use)
Advise Individualize and strongly urge a healthy lifestyle
Agree and Assess Determine patient’s willingness to modify behavior, agree on goals and treatment plan


Aid in developing a tailored intervention
Arrange Schedule follow-up contacts and offer support


Controlling Hypoglycemia. When working with a patient to tailor a diabetes management program, physicians/clinicians should aim to strike a balance between achieving glycemic control and limiting episodes of hypoglycemia. To this end, the ADA has noted that, “Severe or frequent hypoglycemia is an absolute indication for the modification of treatment regimens, including setting higher glycemic goals,”74 and that hypoglycemia should be avoided in older adults with diabetes (Evidence Rating: B).33 Hypoglycemia manifests with various symptoms (Table 5) and can occur suddenly. While mild hypoglycemia may be inconvenient or frightening, severe hypoglycemia can lead to seizures or coma, causing falls, motor vehicle accidents, or other injury.75 


Patients with diabetes must learn to recognize symptoms that presage a hypoglycemic episode. Family physicians, primary care physicians, and other healthcare providers, in turn, must assess their elderly patients’ functional status and discuss with the patient the degree to which he or she experiences such episodes. To assist with this process, the ADA and the Endocrine Society have created a hypoglycemia patient questionnaire and a physician/clinician documentation checklist that are useful tools in primary care.76


Hypoglycemia can be treated by ingesting foods that contain glucose (e.g., fruit, fruit juice, honey) or carbohydrates (e.g., bread, rice, pasta, vegetables, yogurt, milk), with the former being preferred if readily available. However, patients must learn to recognize situations that increase their risk of hypoglycemia (e.g., fasting, exercise, sleep) and take precautions accordingly (e.g., bedtime snacks to prevent overnight hypoglycemia, exercise management, medication adjustments, glucose monitoring). 


Table 5. Symptoms Commonly Associated with Hypoglycemia75

During Waking Hours:

  • Hunger
  • Shakiness
  • Nervousness
  • Sweating
  • Dizziness or light-headedness
  • Sleepiness
  • Confusion
  • Difficulty speaking
  • Anxiety
  • Weakness
  • Palpitations (tachycardia)

During Sleep:

  • Crying out or having nightmares
  • Finding pajamas or sheets damp from perspiration
  • Feeling tired, irritable, or confused after waking up



*The PCMH is based on a “partnership” between the patient and healthcare providers that incorporates skills such as problem solving, decision making, resource utilization, action planning, and self-tailoring of interventions.

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