Diabetes is a chronic disease of the pancreas in which the body cannot regulate the blood sugar level. This is caused if either the body cannot produce its own insulin (known as Insulin Dependent Diabetes or Type 1 Diabetes) or the body stops responding to insulin (known as Non-Insulin Dependent Diabetes or Type 2 Diabetes). According to the UN, about 347 million people around the world have diabetes. The UN confirms that of all diabetic patients, about 90% suffer from Type 2 Diabetes. These patients account for the multi-billion dollar diabetes drug market.
The rise and fall of Blockbusters
For the past many years, Metformin has been indicated, with diet and exercise, as a first line therapy to improve glycemic control in adult patients with type II diabetes. Metformin has a good safety and efficacy profile and is prescribed by many physicians as the first drug of choice while starting an anti-diabetic therapy. When metformin is not enough to help manage a patient’s condition, doctors add one of the several other drugs to lower blood sugar.
In 1999, GSK’s Avandia (generic name rosiglitazone) received the FDA approval to market the drug for patients with type 2 diabetes. The drug was aggressively promoted. For more than half a decade Avandia reigned the market and registered substantial sales. And then the year 2006 saw the launch of the 1st Dipeptidyl peptidase inhibitor (DPP IV Inhibitor), Januvia, by Merck (generic name sitagliptin). The drug had barely made a mark when a meta-analysis highlighting the risk of myocardial infarction and death from cardiovascular causes from rosiglitazone was published in The New England Journal of Medicine. The impact of the report was strongly felt in the medical community as it created opportunities for the newer anti-diabetic agents.
The end result was that Januvia majorly gained from patients switching from Avandia. In 2008, a report by Decision Resources outlined that nearly three-quarters of physicians said that they had switched patients to Merck’s Januvia as a result of the Avandia meta-analysis and more than 80% of surveyed physicians said that they will increase the number of total prescriptions they wrote for Januvia over the next two years 1. With this came the era of DPP4 inhibitors and Januvia along with Janumet (sitagliptin+ metformin) set the cash registers ringing. However, in 2009, the FDA issued a safety alert that linked sitagliptin to acute pancreatitis. By 2011, FDA had received almost 200 reports of acute and chronic pancreatitis linked to Januvia and Janumet – some of which were fatal. A few years later, buzz around a new class of anti-diabetic drugs called the sodium glucose co-transporter or SGLT2 inhibitor was noted. In March 2013, Invokana from J&J (generic name canagliflozin) received an FDA approval. The sodium-glucose co-transporter-2 (SGLT2) is a low-affinity transport system that is specifically expressed in the kidney and plays an important role in renal glucose reabsorption in the proximal tubule. SGLT2 inhibitor thus enhances glucose loss through the urine 2. However, it is still too early to comment anything about SGLT2 inhibitors.
Recently, in June 2013, a second look at a Glaxo study on Avandia’s heart risk led a majority of the 26 members of an FDA advisory panel to recommend either modifying or removing the limits on prescribing and taking Avandia 3. However, this reprieve might be regarded as too little too late as the drug lost its patent protection 2011. It is safe to say that the drug lost some of the most important years in its life-cycle due to the claimed risks in the meta-analysis article as the sales of the once billion-dollar drug plummeted. A few weeks ago, Merck issued a statement saying that it will be participating in the NIDDK-NCI Workshop on Pancreatitis-Diabetes-Pancreatic Cancer which was started recently. The company announced that it welcomes the independent review of the safety profile of Januvia® and other diabetes medicines 4.
The big question
The anti-diabetic drug market is a multi-billion dollar market where one drug’s failure becomes potentially a competitor’s success factor. Pharma giants gain from their opponent’s losses. Sooner or later concerns about safety profiles of the drugs are raised and the sales of once a blockbuster drug come to a standstill. No one’s sure whether these concerns are valid or not, but in the current scenario, both Avandia and Januvia’s safety profiles raise some eyebrows. What’s interesting is to see that all such safety risks (like that of Avandia and Januvia) have come into light more or less around the same time-frame when a new class of drugs is about to be launched in the market. But then, what about Metformin? Isn’t it still the drug with the best safety and efficacy profile? How about the good old way of checking hyperglycemia with metformin coupled with diet and exercise?
In an attempt to compare the long-term benefits and risks of four widely used diabetes drugs in combination with metformin, the NIH initiated the GRADE study (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness). The study began recruitment in June 2013 and aims to enroll about 5,000 patients. This study will help understand how different combinations of medications affect the disease over time, and ultimately help physicians make better choices for their patients’ long-term care 5. Analysts around the world are speculating about the possible outcomes of the study. But only time will tell what’s in store for the patients.
- Concern from doctors regarding the cardiovascular safety of GlaxoSmithKline’s Avandia increases nine-fold following publication of meta-analysis
- Sodium-glucose co-transporter-2 inhibitors: an emerging new class of oral antidiabetic drug
- Glaxo May Get Avandia Reprieve After FDA Panel Vote on Risks (1)
- NIDDK-NCI Workshop on Pancreatitis-Diabetes-Pancreatic Cancer
- NIH begins recruitment for long-term study of diabetes drug efficacy