A Diabetes Study in Japanese Patients   (March 18, 2014)

A recent press story, Adding Vildagliptin to Metformin Improves Glycemic Control superficially sounds like an important scientific advance. The study, titled Efficacy and Safety of Vildagliptin as Add-on to Metformin in Japanese Patients with Type 2 Diabetes Mellitus , has a study design that's frequently used for diabetes drug development (it's a multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-arm study) where one arm of the study included 69 Japanese T2DM patients who were inadequatedly controlled on metformin therapy and received vildagliptin; the other arm had 70 patients who received placebo instead of vildagliptin. The results unsurprisingly showed that the patients getting metformin plus vildagliptin did better than those receiving metformin plus placebo.

Studies like this, where patients already on one diabetes drug get randomized to either placebo or another class of diabetes drug, are a dime-a-dozen. For good reason: like the present study, they routinely show that whatever the other class of diabetes drug that's added, adding an additional drug works better than giving patients a placebo. It's not a big deal; it's a standard way for drugmakers to show regulatory authorities that their diabetes drug (whatever drug it might be) has efficacy greater than placebo, while minimizing risk to the subjects in the study.

Anyway, the combination of vildagliptin (which has at least two brand names, Galvus and Equa, and which is a DPP-4 inhibitor that's not available in the US) plus metformin has already been approved in countries such as the UK (where it's sold as Eucreas) and Australia (sold as Galvumet).

So why did anyone spend the time and money to study a well-understood combination of drugs in Japanese patients? The answer is simple -- it's explained at the ClinicalTrials.gov page for this study - "This study is being conducted to support registration of the fixed-dose combination of vildagliptin and metformin for the treatment of Type 2 diabetes mellitus (T2DM) in Japan."

It seems that the Japanese drug regulators traditionally insist on having studies done on Japanese patients before they are willing to approve a drug, or in this case, a combination of drugs, for use in Japan. Thus, if a drugmaker has done studies on a drug in other parts of the world, they must also answer questions from the Japanese regulators such as "Are there no significant differences in the efficacy and safety caused by ethnic factors (when foreign clinical data are submitted as the pivotal confirmatory data)?" and "Have any specific risks been recognized in the Japanese population?"

And you, gentle reader, thought it was difficult and expensive to get a drug approved by the FDA! (Yes, it is, but in Japan, it's worse.)