medwireNews: Adding the glucagon-like peptide (GLP)1 analog semaglutide to an existing sodium-glucose cotransporter (SGLT)2 inhibitor improves glycemic control and bodyweight in patients with poorly controlled type 2 diabetes, SUSTAIN 9 data show.
During the phase III trial, patients randomly assigned to receive once-weekly subcutaneous semaglutide 1.0 mg (n=151) in addition to their existing SGLT2 inhibitor experienced a mean 1.5% reduction in glycated hemoglobin (HbA1c), from a baseline average of 8.0% (64.1 mmol/mol), after 30 weeks of treatment.
This was significantly greater than the 0.1% reduction, from a baseline of 8.1% (64.5 mmol/mol), observed among the patients randomly assigned to receive placebo (n=151) and resulted in an estimated treatment difference of 1.4% (15.6 mmol/mol).
Furthermore, 78.7% of patients in the semaglutide group achieved an HbA1c below 7.0%, and the researchers calculated that patients in the semaglutide group were 27.3 times more likely to achieve this target and 41.9 times more likely to reach an HbA1c level below 6.5% than those in the placebo group.
As reported in The Lancet Diabetes & Endocrinology, patients receiving semaglutide also experienced significantly greater weight loss than those receiving placebo, at a mean of 4.7 kg versus 0.9 kg, from baselines values of 89.6 kg and 93.8 kg, respectively, giving an estimated treatment difference of 3.8 kg.
The proportion of patients achieving at least 5% and at least 10% weight loss were 49.9% and 15.1%, respectively, with semaglutide and 8.2% and 1.4%, respectively, with placebo.
Reductions from baseline to week 30 in mean BMI, waist circumference, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations were also significantly greater with semaglutide than with placebo, report Bernard Zinman (Mount Sinai Hospital, Toronto, Ontario, Canada) and co-investigators.
Adverse events occurred in 69.3% of patients in the semaglutide group and 60.3% of those in the placebo group. These were generally of mild or moderate severity and most commonly due to gastrointestinal causes, the team observes. Four patients receiving semaglutide developed severe or blood glucose-confirmed hypoglycemia and 13 stopped treatment due to an adverse event compared with none and three, respectively, in the placebo group.
Zinman et al conclude that their findings “are consistent with those of previous trials in the SUSTAIN programme, showing that the addition of semaglutide to existing antidiabetic treatment significantly improves glycaemic control and promotes weight loss.”
In addition to being consistent with previous SUSTAIN data, Stefano Del Prato, from the University of Pisa in Italy, points out in an accompanying commentary that the results also “corroborate those of AWARD-10 and DURATION-8, which explored dulaglutide as an add-on to SGLT-2 inhibitors or simultaneous administration of exenatide (once weekly) and dapagliflozin (once daily), respectively, and support the glucose-lowering efficacy of this combination.”
He says: “Adding semaglutide to SGLT-2 inhibitors addresses part of the pathophysiological complexity of type 2 diabetes, eliciting complementary mechanisms of action that affect glucose control and bodyweight, with an acceptable tolerability and safety profile.”
Del Prato also points out that both medication classes have been shown to be cardioprotective but concludes that “future studies are needed to explore to what extent this combination can provide a more comprehensive cardiovascular benefit.”
By Laura Cowen
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