Miriam E Tucker

May 16, 2015

Nashville, Tennessee — A novel glucose- and lipid-lowering drug that is currently available only in India demonstrated efficacy and safety in a 9-month multicenter postmarketing study.

The findings were presented May 15, 2015 here at the American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress by Shashank R Joshi, MD, an endocrinologist who practices at several hospitals in India and is president of the Indian Academy of Diabetes and president-elect of the Endocrine Society of India.

The drug, a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist called saroglitazar, is not currently available outside India, where it was approved in September 2013 under the brand name Lipaglyn (Zydus Cadila). The manufacturer is seeking a partner to bring the drug to both developed and developing countries for several indications, including "diabetic dyslipidemia," nonalcoholic fatty-liver disease (NAFLD), and lipodystrophy.

"It will be the first time a new chemical entity from India will be used across the world. It's not just a glucose-lowering and a lipid-lowering agent. It may have a potential role in NAFLD and lipodystrophy. I feel this drug is likely to be used around the world....I think it's very exciting," Dr Joshi told Medscape Medical News.

Although saroglitazar is a PPAR agonist, its structure differs from those of the thiazolidinediones (glitazones), fibrates, and even other glitazars that have been developed in the past but have failed to make it to market. It doesn't appear to cause the weight gain or edema seen with many of those agents, Dr Joshi said during his presentation.

Asked for comment, session moderator Janet McGill, MD, professor of medicine at Washington University, St Louis, Missouri, told Medscape Medical News, "It's an interesting compound approved only in India. Our information base is somewhat limited….There seem to be more off-target toxicity problems with the PPARs in general, so it will be interesting to see how this story evolves. But pioglitazone is considered safe, and fibrates are safe. And there's a high bar for approval [in the United States]."

Multiple Effects

In the study reported by Dr Joshi, 787 patients with "diabetic dyslipidemia" were prescribed saroglitazar at the approved 4-mg once-daily dose, by 54 consultant endocrinologists in India. Just 19% were using it as monotherapy, and 51% used it in combination with just one other diabetes medication.

At 9 months, triglycerides were reduced by 44% (from 298 mg/dL at baseline to 156 mg/dL) and non-HDL cholesterol dropped by 30% (199 mg/dL to 132 mg/dL), both significant (P < .0001).

Total cholesterol and LDL cholesterol were both significantly reduced, by 23% and 18.5%, respectively (both P < .0001).

And there was statistically significant improvement in HDL-C from a mean of 41 mg/dL at baseline to 44.5 mg/dL at 9-month follow-up.

Average HbA1c levels, recorded for 695 patients, dropped from 8.5% at baseline to 7.0% at 9 months, also highly significant (P < .0001).

Fasting plasma glucose levels were reduced by 28% (from 172 mg/dL to 117 mg/dL), and postprandial glucose values dropped by 35% (244.5 mg/dL to 149 mg/dL), again significant (P < .0001).

Body weight didn't change over the 9 months (mean (73.9 kg at baseline vs 72.4 kg at 9-month follow-up), and there were no serious drug-related adverse events.

Results were similar in subgroup analyses looking at patients with HbA1c levels above and below 7% and those with and without ongoing diabetes medications at study entry, Dr Joshi reported.

In response to an audience member's question about how these observational results compared with those of the three pivotal randomized controlled trials that were the basis for the drug's approval in India, Dr Joshi acknowledged that those results were "not as robust."

However, he said, "But they're similar. You will always see a little more robust response in postmarketing surveillance. But even [in the randomized trials] the results were attractive."

Dr McGill commented to Medscape Medical News, "This observational trial was 9 months in duration, but according to the author provided more robust results than the registration trials. So, it's not clear how this 9-month observational trial fits into the total picture for this drug. However, it does appear to be promising."

The study was funded by Zydus Cadila. Dr Joshi disclosed receiving grants, research support, and advisory-board, consultant, or speaker support from Abbott, MSD, Novartis, Boehringer Ingelheim, the Public Health Foundation of India, Novo Nordisk, Sanofi, Sun-Ranbaxy, Marico, UpToDate, CMED, Serdia, Pfizer, Johnson & Johnson, DRL, Cipla, Zydus, Bayer-Zydus, and Takeda. Dr McGill reports that she has received research grant support from Andromeda Biotech, Novartis, and Pfizer; speaker honoraria from Abbott Laboratories, AbbVie, AstraZeneca, Boehringer Ingelheim/Eli Lilly, Janssen Pharmaceuticals, Mannkind, and Merck; and research grant support and speaker honoraria from Novo Nordisk and Sanofi.

American Association of Clinical Endocrinologists' 2015 Annual Scientific and Clinical Congress; May 15, 2015; Nashville, Tennessee. Abstract 1233.

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