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Semaglutide plus basal insulin reduces HbA1c, body weight in type 2 diabetes
Adults with poorly controlled type 2 diabetes despite stable basal insulin therapy who were assigned add-on once-weekly semaglutide experienced significant reductions in HbA1c and body weight over 30 weeks vs. those assigned placebo, according to findings from the SUSTAIN 5 trial.
“This study demonstrates that even in patients with longstanding diabetes uncontrolled on insulin, significant improvements in glycemic control, as evidenced by improved HbA1c, can be achieved with a once-weekly injection of semaglutide,” Helena W. Rodbard, MD, FACP, MACE, medical director of Endocrine and Metabolic Consultants in Rockville, Maryland, and a past president of the American Association of Clinical Endocrinologists and the American College of Endocrinology, told Endocrine Today. “In addition, statistically and clinically, weight loss was achieved.”
For SUSTAIN 5, a randomized, double-blind, placebo-controlled trial, Rodbard and colleagues analyzed data from 396 patients with type 2 diabetes recruited from 90 sites in Germany, Japan, Serbia, Slovakia and the United States between December 2014 and November 2015. Participants were receiving stable basal insulin therapy (minimum of 0.25 IU/kg per day) alone or combined with metformin for 90 days before screening, with HbA1c between 7% and 10% (mean baseline HbA1c, 8.4%; mean diabetes duration, 13.3 years). Researchers randomly assigned patients to semaglutide 0.5 mg (Ozempic, Novo Nordisk; n = 132; 56% men; mean age, 59 years), semaglutide 1 mg (n = 131; 58.8% men; mean age, 59 years) or placebo (n = 133; 53.4% men; mean age, 59 years) for 30 weeks as an add-on to background therapy, followed by a 5-week follow-up period. Participants with HbA1c less than 8% at screening had their background basal insulin reduced by 20% at the start of trial medication to limit potential hypoglycemia, according to researchers. Primary outcome was change in HbA1c from baseline to week 30. Secondary endpoint was change in body weight from baseline to week 30, plus several secondary efficacy endpoints, including proportion of patients who achieved HbA1c less than 7% by week 30 and proportion of patients who achieved HbA1c less than 7% without severe hypoglycemia and with no weight gain at week 30.
At week 30, researchers observed mean HbA1c decreases of 1.4% for participants in the 0.5-mg semaglutide arm and 1.8% for those in the 1-mg arm vs. a 0.1% mean decrease for those assigned placebo. The estimated treatment difference vs. placebo was –1.35% (95% CI, –1.61 to –1.1) for semaglutide 0.5 mg and –1.75% (95% CI, –2.01 to –1.5) for semaglutide 1 mg (P < .0001 for both).
At week 30, participants in both the 0.5-mg and 1-mg semaglutide arms experienced greater weight loss vs. those assigned placebo, with estimated treatment differences of –2.31% (95% CI, –3.33 to –1.29) in the 0.5-mg arm and –5.06% (95% CI, –6.08 to –4.04) in the 1-mg arm. Body weight reductions of at least 5% were achieved by 42% of the 0.5-mg group, 66% of the 1-mg group and 11% of the placebo group.
Researchers observed severe or blood glucose-confirmed hypoglycemic episodes in 11 patients in the semaglutide 0.5-mg arm (17 events), 14 patients in the 1-mg arm (25 events) and seven patients in the placebo arm (13 events). The estimated rate ratio for severe or blood glucose-confirmed hypoglycemia was 2.08 (95% CI, 0.67-6.51) for semaglutide 0.5 mg vs. placebo and 2.41 (95% CI, 0.84-6.96) for semaglutide 1 mg vs. placebo.
The most frequently reported adverse events were gastrointestinal, according to researchers, with 11.4% in the semaglutide 0.5-mg arm, 16.8% in the semaglutide 1-mg arm and 4.5% in the placebo arm reporting nausea. Serious adverse events were reported by 6.1% in the semaglutide 0.5-mg arm, 9.2% in the 1-mg arm and 6.8% in the placebo arm. Researchers confirmed neoplasms in four patients receiving 0.5 mg semaglutide and in one patient assigned placebo, and one malignant neoplasm in a patient assigned 1 mg semaglutide.
“The practical implication of this study is that with the addition of semaglutide to insulin, nearly two-thirds of the patients reached an HbA1c of 7% with the lower dose of semaglutide and more than three-fourths reached this goal with the higher dose of semaglutide,” Rodbard said. “As an investigator, it was very gratifying to observe the beneficial effects of the medication and the patient satisfaction with the treatment.”
The researchers noted that, compared with placebo, severe or blood glucose-confirmed symptomatic episodes were more frequent with semaglutide in patients with HbA1c at 8% or lower at screening, which might be expected given the improvements in HbA1c in these patients vs. placebo.
“A greater pre-emptive insulin dose reduction — greater than the 20% mandated protocol in this trial — may be appropriate when titrating from 0.5 [mg] to 1 mg in clinical practice,” the researchers wrote. – by Regina Schaffer
For more information:
Helena W. Rodbard, MD, FACP, MACE, can be reached at Endocrine and Metabolic Consultants, 3200 Tower Oaks Blvd., Suite 250, Rockville, MD 20852; email: hrodbard@comcast.net.
Disclosures: Novo Nordisk funded this study. Rodbard reports she has received grant support and consultant fees from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk and Sanofi. Please see the study for the other authors’ relevant financial disclosures.