Obesity Interventions

Obesity is regarded as a “disease with genetic, environmental and behavioral determinants.” Rather than a BMI-centric approach for treating patients who are obese or overweight, the algorithm emphasizes a “complications-centric model.”1 Patients who will benefit most from medical or surgical interventions have obesity-related comorbidities—ie, either insulin resistance/cardiometabolic disease and/or biomechanical consequences of excess body weight. Weight loss goals are determined by complications, regardless of BMI, and patients should be assessed at three-month intervals to see if they are reaching their goals. Beyond lifestyle therapies, weight loss medications can be used for patients with BMI ≥27 kg/m2 and comorbidities.1 (Table 4)

Prediabetes Pharmacotherapy


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Prediabetes “reflects the failing pancreatic islet beta-cell compensation for an underlying state of insulin resistance, most commonly caused by excess body weight or obesity.”1 The current criteria include impaired glucose tolerance, impaired fasting glucose, or metabolic syndrome. Although weight loss reduces insulin resistance, can prevent progression to diabetes, and can improve plasma lipid profile and blood pressure (BP), it may not directly address the pathogenesis of declining beta-cell function. When indicated, bariatric surgery can be effective in helping to prevent progression from prediabetes to type 2 diabetes (T2D). No medications are FDA-approved solely for the management of prediabetes, but antihyperglycemic medications (eg, metformin and acarbose) do reduce the risk of future diabetes by 25% to 30%, are relatively well tolerated and safe, and may also confer cardiovascular risk benefit.1

T2D Pharmacotherapy

In patients with T2D, “achieving the glucose target and A1C goal requires a nuanced approach that balances age, comorbidities, and hypoglycemia risk” and must be highly individualized.1 For example, in adults with recent-onset T2D and no clinically significant cardiovascular disease (CVD), an A1C of between 6.0% and 6.5% may reduce lifetime risk of micro- and macrovascular complications. However, a “less stringent” A1C of 7.0% to 8.0% may be more appropriate in older patients or those at risk for severe hypoglycemia.1 The order and hierarchy of recommended medications and usage as outlined in the Glucose Control Algorithm are found in Table 5.

Insulin Therapy

The decision to initiate insulin and which type to choose is complex and “depends on each patient’s motivation, cardiovascular and end-organ complications, age, general well-being, risk of hypoglycemia, and overall health status, as well as cost considerations.”1 Patients who are taking two oral antihyperglycemic agents, have an A1C >8.0% and/or long-standing T2D are unlikely to reach their goals with either a third oral agent or even with a GLP-1 RA. A single daily dose of basal insulin should be added to their regimen. Basal insulin analogs provide a flat serum insulin concentration for up to 24 hours, and are preferable to neutral protamine Hagedorn (NPH) insulin. If glycemic goals are not met through use of basal insulin, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium glucose cotransporter-2 inhibitor (SGLT-2i), or a dipeptidyl peptidase 4 inhibitor (DPP-4i) may be added to the regimen.1