Glucagon-Like Peptide-1 Receptor

In overweight adolescents, weekly semaglutide injections plus “lifestyle intervention” resulted in an average reduction in BMI of 16% compared to a reduction of 0.6% with the lifestyle intervention alone at 68 weeks. GI side effects occurred in 62% of the semaglutide group and 42% of the lifestyle alone group. James W. Mold, MD, MPH

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BACKGROUND
A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking.

METHODS
In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68.

RESULTS
A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was −16.1% with semaglutide and 0.6% with placebo (estimated difference, −16.7 percentage points; 95% confidence interval [CI], −20.3 to −13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group.

CONCLUSIONS
Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189. opens in new tab.)

Author/s:

Weghuber, D., Barrett, T.

GLP1Agonists and SGLT2 Inhibitors Table

Saige Blanchard — Thu, 10 Mar 2022 06:00:00 +0000

Date Added:

March 10, 2022

Publication Date:

February 6, 2022

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Poster

MeSH

diabetes mellitus, type 2

Sodium-Glucose Transporter 2 Inhibitors

Glucagon-Like Peptide-1 Receptor

Patient Selection

This table shows the relative risk reduction (RRR) and absolute risk reduction (ARR) as percentages for GLP1 agonists and SGLT2 Inhibitors, based upon RCTs of at least one year duration. In most cases, the participants were at high risk for adverse CV events, but the ARRs were still fairly small, with insufficient information about how these drugs perform vs. other, less expensive antihyperglycemic agents. James W. Mold, MD, MPH

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Based upon the following two meta-analyses:
1. Alexander JT, et al. The longer-term benefits and harms of glucagon-like peptide-1 receptor agonists: A Systematic review and meta-analysis. JGIM, 2021; 7(2): 415-43.
2. Alexander JT, et al. Longer-term benefits and risks of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: A systematic review and meta-analysis. JGIM, 2021; 37(2): 439-44, plus Supplementary materials at https://doi.org/10.1007/s11606-021-07227-0.

Selection criteria for the RCTs was that the study period was at least 52 weeks in duration. I assume the average duration of the studies was at least 2 years. So, an absolute risk reduction of mortality of 0.5% would be per 2+ years.

Author/s:

Mold, J. W.

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

John Bayhi — Tue, 26 May 2020 20:43:16 +0000

Date Added:

May 26, 2020

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 22, 2020

Volume:

Online ahead of print

URL:

Using Insulin to Treat Poorly Controlled Type 2 Diabetes in 2020

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2020.1303

Keywords

PMID (1):

32442246

MeSH

Sodium-Glucose Transporter 2 Inhibitors

hypoglycemic agents

insulin

glycated hemoglobin a

dipeptidyl-peptidase IV inhibitors

Metformin

diabetes mellitus, type 2

Glucagon-Like Peptide-1 Receptor

Thiazolidinediones

A potentially useful decision algorithm for management of patients with Type 2 diabetes, which includes early consideration of use of basal insulin in patients with A1c > 9%. James W. Mold, MD, MPH

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No abstract available

Author/s:

Hirsch, IB, Gaudiani, LM