Body Weight Considerations in the Management of Type 2 Diabetes

Abstract

Obesity is one of the main risk factors for type 2 diabetes (T2D), representing a major worldwide health crisis. Modest weight-loss (≥ 5% but < 10%) can minimize and reduce diabetes-associated complications, and significant weight-loss can potentially resolve disease. Treatment guidelines recommend that intensive lifestyle interventions, pharmacologic therapy, and/or metabolic surgery be considered as options for patients with T2D and obesity. The benefits and risks of such interventions should be evaluated in the context of their weight-loss potential, ability to sustain weight change, side effect profile, and costs. Antihyperglycemia therapies have considerable effects on patient weight, prompting careful consideration of weight-loss or weight-neutral therapies for patients with T2D who also have obesity. Metformin, sodium glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), α-glucosidase inhibitors, and amylin mimetics promote weight-loss. Dipeptidyl peptidase-4 inhibitors and fixed-ratio insulin/GLP-1 RA combination therapies (IDegLira, iGlarLixi) appear to be weight-neutral. Thiazolidinediones, insulin secretagogues (sulfonylureas, meglitinides), and insulins are associated with weight gain. Sulfonylureas are additionally associated with a higher risk of serious hypoglycemia from hyperinsulinemia, making them less suitable for the treatment of patients who are overweight or have obesity. Patients are often overtitrated on basal insulin, resulting in an increased risk of hypoglycemia and weight gain without achieving glycemic goals. Given these observations, the effects of antihyperglycemia agents on weight should be considered when individualizing T2D therapy.Funding: Sanofi US, Inc.

Keywords: Antihyperglycemia therapy; GLP-1 RA; Insulin; Lifestyle; Obesity; Type 2 diabetes; Weight management; Weight-loss.

Fig. 1

Complex pathophysiology of obesity and type 2 diabetes. GIP glucose-dependent insulinotropic polypeptide (gastric inhibitor polypeptide), GLP-1 RA glucagon-like peptide-1 receptor agonist, NEFA non-esterified fatty acids Reproduced with permission from Scheen AJ, Van Gaal LF. Lancet Diabetes Endocrinol. 2014;2:911–922. [3] © 2014 Elsevier Ltd. All rights reserved

Fig. 2

Profiles of antidiabetic medications. AGI alpha-glucosidase inhibitor, ASCVD atherosclerotic cardiovascular disease, BCR-QR bromocriptine qui release, CHF congestive heart failure, COLSVL colesevelam, DPP-4i dipeptidyl peptidase 4 inhibitor, FDA US Food and Drug Administration, GI Sx gastrointestinal side effects, GLN glinides, GLP-1 RA glucagon-like peptide-1 receptor agonist, MET metformin, PRAML pramlintide, SGLT-2i sodium glucose co-transporter 2 inhibitor, SU sulfonylurea, TZD thiazolidinedione Reprinted with permission from American Association of Clinical Endocrinologists © 2018 AACE. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE/ACE comprehensive type 2 diabetes management algorithm 2018. Endocr Pract. 2018;24:91–120