Research round-up: medications for type 2 diabetes
medwireNews: One of the final sessions on Saturday featured the presentation of new, and mostly positive, data on medications for glycemic control in patients with type 2 diabetes.
The first presentation, simultaneously published in JAMA Psychiatry, focused on patients with schizophrenia. Presenter Louise Vedtofte (University of Copenhagen, Denmark) stressed that around 15% of patients with schizophrenia develop diabetes, making it an important problem to address.
Her team’s research revealed that liraglutide significantly improved oral glucose tolerance test results, and reduced bodyweight in patients with severe schizophrenia. The 47 patients randomly assigned to receive liraglutide 1.8 mg/day for 16 weeks had an average bodyweight reduction of 4.7 kg, compared with a 0.5 kg increase in the 50 patients taking placebo.
All the patients were taking the antipsychotics olanzapine or clozapine, which Vedtofte said are associated with a high risk for weight gain, with patients often gaining 10–20 kg in a year; the study participants had an average starting body mass index of around 34 kg/m2. These antipsychotics are reserved for the hardest to treat patients, leaving them “trapped on medication which is good for their mental health, but which is detrimental to their somatic health.”
Nausea was more frequent in the liraglutide group, but was transient, occurring mostly during the up-titration period.
Two other trials presented in this session featured the in-development sodium glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin: the VERTIS FACTORIAL and VERTIS SITA2 extension trials. The researchers previously reported positive data for 26 weeks’ follow-up; the latest findings tested the durability of the effect out to 52 weeks.
VERTIS FACTORIAL, presented by Richard Pratley (Florida Hospital Diabetes Institute, Orlando, USA), tested ertugliflozin (5 or 15 mg/day) plus sitagliptin 100 mg/day versus each treatment alone in patients with poor glycemic control on metformin (glycated hemoglobin [HbA1c] 7.5–11.0%). And VERTIS SITA2, presented by Jie Liu (Merck & Co. Inc, Chicago, Illinois, USA), tested ertugliflozin in patients with poor glycemic control on metformin plus sitagliptin.
In neither trial did the ertugliflozin dose seem to affect the results, with both doses achieving similar improvements in HbA1c. In VERTIS FACTORIAL, combination treatment produced an HbA1c reduction of nearly 1.4%, compared with just under 1% for the ertugliflozin doses individually and 0.8% with sitagliptin. Combination treatment also benefited bodyweight and blood pressure relative to sitagliptin treatment alone.
Next, Shin-ichi Harashima (Kyoto University, Japan) presented data showing the efficacy of canagliflozin in insulin-dependent Japanese patients. He reported a 1.10% difference in HbA1c levels favoring active treatment between 76 patients assigned to canagliflozin and 70 taking placebo, after 16 weeks of treatment. Patients in the placebo group then switched to canagliflozin, with similar results. There was an increased rate of hypoglycemia in patients after they had initiated canagliflozin, but this decreased after their insulin doses were adjusted.
The presentation by Juan Frias (National Research Institute, Los Angeles, California, USA) featured data from DURATION-7, in which the glucagon-like peptide-1 receptor agonist exenatide was given to insulin-dependent patients, after an 8-week run-in during which basal insulin dose was optimized, and any sulfonylureas were stopped (metformin was continued). At this point, the patients’ average HbA1c level was 8.5%. After 28 weeks of treatment, this was 0.7% lower in the 231 patients taking exenatide than in the 230 taking placebo. Exenatide treatment also produced a 25 percentage point increase in the proportion of patients achieving their HbA1c target and improvements in post-prandial glucose, fasting plasma glucose, and bodyweight.
The only negative results of the session were presented by Ankut Shah (Columbia University, New York, USA), whose team had hoped that sitagliptin treatment could tackle recurrent or persistent diabetes in patients after Roux-En-Y gastric bypass surgery. The treatment did cause an increase in post-prandial glucagon-like peptide-1 levels, but had no effect on post-prandial levels of glucose or insulin.
Yehuda Handelsman (Metabolic Institute of America, Tarzana, California, USA) then discussed a study of the responses of patients with poor glycemic control on metformin who were given a dipeptidyl peptidase-4 inhibitor with or without the SGLT2 inhibitor dapagliflozin.
He reported that HbA1c values fell from 8.8% to 7.3% in the 232 patients given triple therapy (metformin plus saxagliptin plus dapagliflozin) and from 8.9% to 7.6% in the 229 given dual therapy (metformin plus sitagliptin), which was a significant difference in favour of triple therapy. The larger reduction in HbA1c values occurred irrespective of patients’ baseline levels and more patients in the triple therapy group achieved the 7.0% target level (37 vs 25%), added Handelsman.
Patients in the triple therapy group lost more weight, but had an increased risk for urinary tract infections and hypoglycemic events.
And in the final presentation of the day, Liana Billings (NorthShore University Health System, Skokie, Illinois, USA) presented results that a delegate described as “one of the most robust, most impressive pieces of data I have seen in years.” Read our full report of that trial here.
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