Doubling the dose of semaglutide (Ozempic) may be a useful possibility for individuals not reaching glycemic objectives, in line with the SUSTAIN FORTE research.
Within the double-blind section IIIb trial, adults on 2.0 mg of once-weekly injectable semaglutide had a 2.1% imply drop in baseline HbA1c over 40 weeks of therapy versus a 1.9% discount in these on 1.0 mg of semaglutide (estimated therapy distinction [ETD] -0.18%, 95% CI -0.31 to -0.04, P=0.0098 for therapy coverage estimand), reported Juan Pablo Frías, MD, of the Nationwide Analysis Institute in Los Angeles, and colleagues.
The doubled dose of weekly semaglutide was additionally related to higher weight reduction, with a median 6.4 kg discount over 40 weeks in contrast with 5.6 kg for these on the 1 mg weekly dose (ETD -0.77 kg, 95% CI -1.55 to 0.01, P=0.054 for therapy coverage estimand), the group wrote within the research on-line in The Lancet Diabetes & Endocrinology.
Though gastrointestinal hostile occasions have been a bit extra frequent with the bumped-up dose (34% vs 31% for 1.0 mg) — frequent with the GLP-1 receptor agonist class — there wasn’t a big distinction within the fee of significant hostile occasions between the doses (4% vs 5% for 1.0 mg).
Through the trial, three deaths occurred: two within the 2.0 mg semaglutide group and one within the 1.0 group. Each deaths within the 2.0 mg group have been deemed unrelated to the research drug, however the loss of life within the 1.0 mg group was thought of “probably associated to the research product by the investigator and unlikely to be associated to the research product by the sponsor,” the researchers stated.
“Semaglutide 2.0 mg gives a invaluable therapy possibility for people with kind 2 diabetes, along with already out there 0.5 mg and 1.0 mg doses, and could possibly be helpful for these in want of therapy intensification whereas remaining on the present remedy,” the investigators wrote.
Semaglutide first gained FDA approval in 0.5 mg and 1.0 mg injectable dosing offered underneath the commerce identify Ozempic in December 2017 primarily based on the outcomes of the Semaglutide Unabated Sustainability In Therapy of Kind 2 Diabetes (SUSTAIN) scientific trial program. This approval was for a sign of kind 2 diabetes and threat discount of main cardiovascular occasions together with coronary heart assault, stroke, and loss of life in adults with kind 2 diabetes with identified coronary heart illness.
Then in September 2019, an oral type of semaglutide was authorized in 7 and 14 mg tablets, offered underneath the commerce identify Rybelsus, likewise indicated for kind 2 diabetes.
Most lately this previous June, a 2.4 mg injectable dose, offered underneath the identify Wegovy, was authorized for continual weight administration in adults with weight problems — physique mass index (BMI) of 30 or higher — or for adults with obese (BMI of 27 or higher) with not less than one weight-related situation, reminiscent of hypertension, kind 2 diabetes, or excessive ldl cholesterol, used at the side of a lowered calorie food regimen and an train routine.
Nonetheless, the creator of a commentary accompanying the research by Frías and colleagues, André Scheen, MD, PhD, of Liège College in Belgium, wasn’t precisely satisfied by this technique.
“The add-on worth of semaglutide 2.0 mg versus 1.0 mg once-weekly seems moderately poor, when contemplating the incremental reductions in HbA1c and body weight,” he wrote. “The modifications have been statistically important however barely clinically related.”
As a substitute of doubling the dose of the GLP-1 receptor agonist, Sheen steered choosing one other agent when confronted with a affected person struggling to regulate HbA1c.
“As an example a mixture with a SGLT2 inhibitor, a twin remedy that additionally improves glucose management, reduces body weight, lowers blood stress, and has the potential to enhance each cardiovascular and renal outcomes,” he advisable. “To this finish, a pharmacoeconomical comparability utilizing onerous scientific outcomes between a better dose of GLP-1 receptor agonist and such a twin remedy could be of main curiosity.”
The ten-country SUSTAIN FORTE trial was carried out throughout 125 outpatient clinics and included adults with poorly managed kind 2 diabetes — outlined as an Hba1c of 8% to 10% — handled with metformin. About half the 961 members additionally obtained a sulfonylurea. The typical age of members was 58, imply baseline HbA1c was 8.9%, and common BMI was about 35.
Sufferers have been began on a 0.25 mg dose of semaglutide for 4 weeks, adopted by 4 weeks on a 0.5 mg dose; thereafter, the dose was titrated as much as 1.0 mg for one more 4 weeks. Beginning at week 13, members obtained one other pen injection, containing both an extra 1.0 mg of semaglutide or placebo.
One research limitation, Sheen famous, was an absence of information on different surrogate endpoints, together with blood stress and lipids.
Based mostly on the outcomes of the research, sponsor Novo Nordisk resubmitted an application to the FDA in Might 2021 for a label enlargement to incorporate the two.0 mg dose indicated for kind 2 diabetes. This was subsequent to the corporate receiving a Refusal to File letter from the FDA in March 2021 asking for added info, together with knowledge referring to a proposed new manufacturing website. A call is predicted inside 10 months.
Final Up to date July 22, 2021
The trial was funded by Novo Nordisk.
Frías reported monetary relationships with Novo Nordisk, AstraZeneca, Bristol Myers Squibb, Janssen, Novartis, Oramed, Pfizer, Boehringer Ingelheim, Eli Lilly, Merck KGaA, and Sanofi; co-authors additionally reported disclosures, together with with Novo Nordisk.
Scheen reported having served as a scientific investigator within the SCALE and STEP-1 trials of subcutaneous semaglutide.