Katherine H. Saunders, MD Leon I. Igel, MD, FACP, DABOM Alpana P. Shukla, MD, MRCP Louis J. Aronne, MD, FACP, DABOM, FTOS Weill Cornell Medicine, New York, NY kph2001@med.cornell.edu
Drs. Saunders, Igel, and Shukla reported no potential conflict of interest relevant to this article.
Dr. Aronne reported that he is a consultant/advisor to Eisai, Gelesis, GI Dynamics, Jamieson Labs, JOVIA Health, Novo Nordisk A/S, Pfizer Inc, and VIVUS; a shareholder of Gelesis, Jamieson Labs, Myos Corp, and Zafgen; and a member of the board of directors of Gelesis, and Myos Corp. Dr. Aronne also reported receiving research funding from Aspire Bariatrics and Eisai.
The 2016 Comprehensive Type 2 Diabetes Management Algorithm published by the American Association of Clinical Endocrinologists and American College of Endocrinology recommends that the initiation of diabetes therapies be based on the risks of weight gain and hypoglycemia, among other factors. The algorithm calls for metformin as first-line therapy, followed by a GLP-1 agonist as a second-line therapy, and an SGLT2 inhibitor as a third-line therapy.6
Finally, FDA-approved anti-obesity medications may be appropriate for patients with diabetes who are unable to lose weight with lifestyle interventions alone.22 Each medication is associated with improvements in glucose in addition to other metabolic parameters.
CASE 1 ›A better choice for Mr. P
Because Mr. P has gained weight—and, indeed, developed obesity—since he started taking glyburide, it is clear that a sulfonylurea is not the best choice for this patient. An antidiabetic agent that is weight-neutral or that promotes weight loss, such as an SGLT2 inhibitor or a GLP-1 agonist, would be more suitable. The drug should be prescribed in conjunction with his metformin, which has a favorable weight profile and helps reduce HbA1c, as both SGLT2 inhibitors and GLP-1 agonists also do.
If Mr. P were to switch to an SGLT2 inhibitor, a combination pill containing metformin would be an effective way to limit the patient’s pill burden.
Treating hypertension without weight gain
Thiazide diuretics are often recommended as first-line agents for the treatment of hypertension, but their dose-related adverse effects, including dyslipidemia and insulin resistance, are undesirable for patients who are overweight or obese and at risk for metabolic syndrome and type 2 diabetes.23 Beta-adrenergic blockers have been shown to promote weight gain and prevent weight loss, especially in patients who have both hypertension and diabetes.24 In addition to having potential adverse metabolic effects on lipids and/or insulin sensitivity, beta-blockers can decrease metabolic rate by 10% and they may have other negative effects on energy metabolism, as well.25
When a patient who is obese has a condition for which a beta-blocker is a necessity, a selective agent with a vasodilating component is recommended.
In a meta-analysis of 8 RCTs that lasted ≥6 months, changes in body weight were higher in participants on beta-blockers, with a median difference of 1.2 kg (−0.4 to 3.5 kg) between those on beta-blockers and the control group.26 The evidence suggests that beta-blockers should not necessarily be first-line treatment for hypertension in patients who are overweight or obese and that obesity management in patients with hypertension may be harder if they are being treated with a beta-blocker.
