Novel compounds show promise for type 2 diabetes
medwireNews: Study results presented at the EASD annual meeting in Lisbon, Portugal, demonstrated the potential of several novel therapies for the treatment of obesity-related metabolic dysfunction and type 2 diabetes.
Puneet Arora, from Genentech, Inc in San Francisco, California, USA, described the results of a first-in-human phase I study of BFKB8488A, an antibody that regulates bodyweight and glucose lipid metabolism through binding to the fibroblast growth factor-1 complex.
The researchers found that 53 overweight or obese participants with likely insulin resistance who were randomly assigned to receive a single injection of BFKB8488A experienced significant dose-dependent reductions in bodyweight between baseline and day 8, with no accompanying decrease in food consumption or appetite. On the other hand, the 18 participants given placebo had minimal changes in bodyweight over the study period.
Patients receiving the antibody also had dose-dependent decreases in insulin, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increases in high-density lipoprotein cholesterol and adiponectin, from baseline to day 8, and these changes persisted for up to 8 weeks after the injection.
Although 87% of participants reported at least one adverse event, Arora reported that the treatment was “generally well tolerated,” with the majority of adverse events being mild in severity. None of the participants experienced dose-limiting adverse events, and there were no deaths over the course of the trial.
The compound may therefore “have potential utility in the treatment of obesity-related metabolic disorders,” concluded Arora.
Two subsequent presentations in the session focused on the treatment of patients with confirmed type 2 diabetes. A post-hoc analysis of the DUAL II and DUAL V studies, presented by Tina Vilsbøll (Gentofte Hospital, Copenhagen, Denmark), demonstrated that insulin degludec/liraglutide combination therapy (IDegLira) is associated with an improvement in cardiovascular risk markers compared with basal insulin treatment among patients undergoing concomitant treatment with metformin.
In the DUAL II study, patients treated with insulin degludec/liraglutide for 26 weeks had a significantly greater reduction in systolic blood pressure than those who were treated with insulin degludec alone (5.4 vs 1.7 mmHg), in addition to significantly greater weight loss (2.7 vs 0.0 kg) and lower levels of total and LDL cholesterol.
Similarly, in the DUAL V study of insulin degludec/liraglutide versus insulin glargine, those given the combination treatment experienced significantly greater reductions in systolic blood pressure, bodyweight, total cholesterol, LDL cholesterol, and free fatty acids.
The final presentation of the session described a dose-ascending study of MEDI4166, a fusion molecule of an antibody against PCSK9 and glucagon-like peptide 1 (GLP-1).
Meena Jain (MedImmune, Cambridge, UK) and colleagues found that 60% of 30 metformin-treated type 2 diabetes patients who received MEDI4166 at any dose experienced adverse events, compared with 50% of the 10 patients who underwent placebo treatment. There were no deaths, serious adverse events, or adverse events leading to treatment discontinuation, pointing to “an acceptable safety profile,” said Jain.
There was also a dose-dependent reduction in LDL cholesterol levels among patients who were treated with the compound, and pharmacodynamic assessments “suggested dual target engagement of GLP-1 and PCSK9 after a single dose,” she concluded.
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