There was a wealth of interesting new data and concepts presented at the 73rd Scientific Sessions of the America Diabetes Association (ADA), held recently in Chicago, but three areas of research caught my interest in particular: early triple therapy; insulin and GLP-1 combination treatment; and promising data for a novel obesity agent.
Three: triple treatment first
The traditional focus on lowering blood sugar in type 2 diabetes treatment was questioned by data presented during the ADA President's Oral Sessions. In a randomized trial, a pathophysiologically based, triple combination therapy (metformin, pioglitazone and exenatide) targeting the core metabolic defects of type 2 diabetes (insulin resistance and -cell dysfunction) was compared with a conventional step-wise strategy (metformin with subsequent sulphonylurea and insulin therapy) in newly diagnosed patients. The triple therapy demonstrated significant and sustained reductions in HbA1c, compared with similar but not sustained reductions associated with the conventional treatment approach. Moreover, a significantly greater proportion of the triple therapy group achieved HbA1c goals. In addition, the triple therapy was associated with weight loss and a 13.6-fold reduction in hypoglycemia rates, compared with the step-wise treatment approach.
Two: insulin and GLP-1 agonists in combination
In one of the Current Issues oral sessions, two leaders in the field of diabetes, Vivian Fonseca and Alan Garber, presented the rationale for using insulin and GLP-1 agonists, respectively, in patients who are failing on oral antidiabetic medications. Despite putting forward eloquent cases, each speaker came to the same conclusion: the evidence would suggest using both.
The recommendations from these experts were timely for Novo Nordisk, who had new data available for their fixed combination of insulin degludec and liraglutide; for further details on novel fixed combination treatments, see our Diabetes Pharmacor. In a randomized controlled trial, the insulin degludec and liraglutide combination was compared with each individual component. The combination showed significant benefits over insulin alone in terms of HbA1c change, weight loss and hypoglycemia rates, and over liraglutide alone in terms of HbA1c change, fasting plasma glucose levels and gastrointestinal adverse events.
It would appear that rather than having to choose between the injectable antidiabetic agents, physicians may soon have to choose which combination of injectable agents to prescribe.
One: promising new agent for obesity
The currently available treatments for obesity, and even those in late stage development, are all based on existing approaches or combining old drugs, which is why the interim Phase II data presented for beloranib were of particular note. Beloranib is Zafgen's novel methionine aminopeptidase 2 inhibitor, which works through increasing fatty acid oxidation; for further detail see our Obesity Pharmacor. In a double-blind, placebo-controlled study, obese men and women were randomized to 0.6, 1.2, or 2.4 mg of subcutaneous beloranib, or placebo twice-weekly. In this pre-specified interim analysis of the first 19 patients (all white females; mean age 40.3 years, weight 101.2 kg, and BMI 37.9 kg/m2), recipients of the top dose of beloranib achieved a 9.9 kg weight loss, compared with 1.8 kg for placebo (p<0.005) at 12 weeks. Measures of hunger and lipid parameters were also improved with beloranib, and it was considered to be generally well tolerated. Although peer review of the final results is needed, these initial data raise the hope of another agent with potency similar to the most efficacious product on the market, Vivus's Qsymia.
Tim Blackstock, M.B. Ch.B., is a business insights analyst with the Cardiovascular, Metabolic and Renal Disorders team at Decision Resources.
An in-depth analysis of the type 2 diabetes mellitus and obesity therapeutic areas, with accompanying epidemiology driven sales forecast models, are presented in Decision Resource Diabetes and Obesity Pharmacor reports, respectively.