patient care perspectives

Role of Chronic Overweight Therapies in Type 2 Diabetes

by Serena Cardillo, MD

Overview

The approach to overweight and obesity in patients with type 2 diabetes begins with counseling and lifestyle modification, but it often requires additional interventions. Prioritizing weight loss draws on different strategies for different patients.

Expert Commentary

Serena Cardillo, MD

Fellowship Program Director and Director of Education
Professor of Clinical Medicine and Physician
Division of Endocrinology, Diabetes and Metabolism
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA

“When prioritizing weight loss in patients with type 2 diabetes, there should be an early and continued emphasis on counseling and lifestyle modifications, but the approach also involves careful consideration of pharmacotherapy that will help to promote weight loss.”

Serena Cardillo, MD

When prioritizing weight loss in patients with type 2 diabetes, there should be an early and continued emphasis on counseling and lifestyle modifications, but the approach also involves careful consideration of pharmacotherapy that will help to promote weight loss.

First and foremost, it is important to not lose sight of the fundamentals, which include referral to a nutritionist for guidance in dietary modification. Early in the course of disease, approximately within the first decade, it is possible to reverse type 2 diabetes and to eliminate the need for pharmacotherapy. Later, with progressive pancreatic beta cell decline and the requirement for insulin, reversing the disease is less likely; however, weight loss is still beneficial in that the diabetes is more easily managed and the patient has the associated improvements in the metabolic parameters that impact cardiovascular outcomes.

In addition, a basic approach includes the preferential prescribing of medications that will facilitate weight loss and the avoidance of those medications that promote weight gain. If lifestyle changes are not successful, you should consider obesity-specific pharmacotherapy. Early first-line treatments such as metformin can initially promote very mild weight loss, while sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists have also been shown to reduce weight. As a result, careful consideration is given to these classes of medication when prioritizing weight loss in treating patients with type 2 diabetes. US Food and Drug Administration–approved agents for weight loss include several obesity-specific medications, such as the GLP-1 agent liraglutide prescribed at a higher dose than that used for type 2 diabetes treatment. These medications are approved for the indication of weight loss, independent of a diabetes diagnosis. The recent approvals of higher doses of alternate GLP-1–based therapies have also allowed for more targeted weight loss interventions in treating patients with obesity and diabetes.

In addition to prescribing medications that promote weight loss, providers should minimize the use of medications that promote weight gain in this patient population, where possible. These agents include any type of insulin formulation and medications that stimulate insulin secretion such as the sulfonylureas and the meglitinides. Insulin and the secretagogues are associated with increased hunger and hypoglycemia. Excess dosing of basal insulin to meet postprandial excursions will likely result in increased caloric intake as patients consume more in an attempt to “feed their insulin” to prevent hypoglycemia. The thiazolidinediones are also associated with weight gain, as well as fluid retention. While there are certainly clinical situations in which the aforementioned agents are necessary and indicated, these medications may fall lower on an individualized treatment algorithm for those patients for whom weight loss is the priority. Weight neutral medications such as dipeptidyl peptidase-4 inhibitors can also be considered as potential alternatives.

Beyond medical therapy, bariatric surgery is another highly effective approach that has been associated with disease reversal and marked improvement in several metabolic parameters. This should be considered as an option for patients struggling with obesity.

References

American Diabetes Association. Standards of Medical Care in Diabetes-2021 abridged for primary care providers. Clin Diabetes. 2021;39(1):14-43. doi:10.2337/cd21-as01

Apovian CM, Aronne LJ, Bessesen DH, et al; Endocrine Society. Pharmacological management of obesity: an Endocrine Society clinical practice guideline [published correction appears in J Clin Endocrinol Metab. 2015;100(5):2135-2136]. J Clin Endocrinol Metab. 2015;100(2):342-362. doi:10.1210/jc.2014-3415

Giorda CB, Orsi E, De Cosmo S, et al. Prescription of sulphonylureas among patients with type 2 diabetes mellitus in Italy: results from the retrospective, observational multicentre cross-sectional SUSCIPE (Sulphonyl_UreaS_Correct_Internal_Prescription_Evaluation) study. Diabetes Ther. 2020;11(9):2105-2119. doi:10.1007/s13300-020-00871-5

Hodish I. Insulin therapy, weight gain and prognosis. Diabetes Obes Metab. 2018;20(9):2085-2092. doi:10.1111/dom.13367

Kwee LC, Ilkayeva O, Muehlbauer MJ, et al. Metabolites and diabetes remission after weight loss. Nutr Diabetes. 2021;11(1):10. doi:10.1038/s41387-021-00151-6

Leitner DR, Frühbeck G, Yumuk V, et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts. 2017;10(5):483-492. doi:10.1159/000480525

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