A diabetes drug that strikes the right balance

Just a few years after its introduction in the late ’90s, this particular drug quickly became a bestseller. But right after gaining prominence as a revolutionary new approach in treating type 2 diabetes, problems surfaced as numerous studies found that it could raise the risk of heart attack by as much as 40 percent.

Amid findings of several more serious and deadly side effects, Europe decided to ban the drug’s sale last year. On the other hand, the United States this week decided to pull the drug off retail pharmacy shelves and severely restrict its dispensing.

“Indeed, it is a cautionary tale, a reminder for us to look at new drugs from many angles and the need to check and re-check the data. It also shows that in coming up with an ideal drug to manage diabetes, there exist a delicate balancing act,” admitted Dr. James Foley, principal medical and scientific expert in diabetes of Novartis Pharmaceutical’s Global Medical Affairs.

Speaking to Inquirer Health last week, Foley explained that for most, the management of diabetes is a challenge that requires finding the right balance among food, physical activity and medications.

But there’s more to it, according to Foley, who has been recognized as a leading figure in diabetes drug discovery and development.

“In developing the most ideal antidiabetes drug, developers must not only ensure that it is effective in keeping one’s blood sugar level as close to normal as possible—not too high (called hyperglycemia) or too low (called hypoglycemia). The drug must be able to be safely combined with other antidiabetes therapy as well as work in conjunction with other medications,” Foley said.

“It must also show no serious or dangerous side effects, no issues that may affect compliance (like timing and manner of taking the medication or frequency of dosing) and that it should not be prohibitively priced,” he added.

Foley explained that vildagliptin (Galvus) is a product of such careful consideration and analysis since the drug for so many years has been subjected to numerous clinical trials with tens of thousands of patients exposed to the drug.

Numerous trials

“I was involved in its discovery and development and while we were excited about the drug’s mechanism, we had to subject it to numerous trials, combine it with other existing therapies, as well as enroll significant number of patients and observe its long-term effect,” informed Foley, who between 1986 and 1997, was the director of the Diabetes Research Program at Sandoz (the generics arm of Novartis) that invented vildagliptin.

Vildagliptin belongs to a new class of oral diabetes medication that works by inhibiting the enzyme called DPP-4. With DPP-4 inhibited, the drug as a result, raises the levels of a naturally occurring gastrointestinal hormones, called GLP-1 and GIP.

These hormones, in response to high blood glucose levels, are responsible for causing the pancreas to produce more insulin while simultaneously discouraging the liver from producing sugar.

And unlike traditional therapies, vildagliptin does not induce hypoglycemia or even weight gain. In fact, in one study, it was found that patients taking vildagliptin and metformin have 10 times fewer reports of hypoglycemia compared to those taking sulfonylurea glimepiride and metformin.

“Which is why this drug is recommended for patients who do not achieve glycemic control with metformin, cannot tolerate metformin, or have experienced hypoglycemia with sulfonylurea,” said Foley.

He added that patients who can’t tolerate traditional antidiabetes drug can use vildagliptin as a monotherapy (use of a single drug for treatment) or in combination with other antidiabetic drugs. Patients with poor compliance can also try a combination of metformin with vildagliptin.

Available data have also shown that vildagliptin avoids the gastrointestinal side effects of metformin but the weight-gain observed in those taking thiazolidinediones, while cutting insulin requirements by around half.

Most ideal

He said that with an estimated 366 million people around the world suffering from diabetes, vildagliptin may be the most ideal drug that could help majority of these individuals enjoy a better quality of life.

“I know that diabetes could strike individuals as young as 30 years old. But with proper diet, continuous exercise and continuous medication that included vildagliptin, I believe it is possible to provide these young patients a much better health-related quality of life for 50 more years,” Foley said.

With 4.6 million deaths per year due to diabetes, the International Diabetes Federation predicts that within 20 years, the number of people with diabetes could jump to half a billion.

“But vildagliptin is a big leap forward in diabetes care. With vildagliptin, doctors now have a trusted partner that they could easily dispense with and not worry about serious side effects,” Foley explained.