Skill Checkup: A 36-Year-Old Man With Type 2 Diabetes Is Struggling to Lose Weight

Anne L. Peters, MD

Disclosures

June 01, 2022

Although some of the older antidiabetic therapies, such as sulfonylureas and insulin, are associated with weight gain, the sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with weight reduction. In fact, the subcutaneous GLP-1 RAs semaglutide and liraglutide are approved by the US Food and Drug Administration for weight loss in patients with obesity or patients who are overweight with at least one related comorbidity (eg, type 2 diabetes, hypertension).

Other GLP-1 RAs and SGLT2 inhibitors have shown impressive weight reduction over time. At doses used for cardio protection or treatment for congestive heart failure, typical weight reductions are on the order of 3%-5% of body weight. SGLT2 inhibitors have a primary effect on glucose excretion, so calories are lost in the urine, and the patient typically "loses" about 300 calories per day. GLP-1 RAs have both central and peripheral effects. The central effects of GLP-1 RAs suppress appetite and gastrointestinal effects delay gastric absorption, prompting weight loss.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are generally weight-neutral, although modest weight loss has been observed with vildagliptin in patients with relatively low baseline glycemia. The weight neutrality of vildagliptin likely results in part from its intrinsically low risk for hypoglycemia.

Sulfonylureas show high efficacy in lowering A1c (reductions of approximately 1.25% compared with placebo), but are associated with weight gain and hypoglycemia. Owing to associated hypoglycemia, weight gain, and possible cardiovascular risk, together with their diminished efficacy over time, sulfonylureas should be avoided in patients with obesity.

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