Nateglinide Plus Metformin Good Initial Combo for Type 2 Diabetes

Study highlighted the importance of the postprandial period in overall glycemic exposure.”

For patients with type 2 diabetes, initial treatment with metformin plus either nateglinide or glyburide provides similarly good glycemic control for at least 2 years, but the nateglinide/metformin combination appears to be the safer approach.
"The glyburide/metformin combination is associated with a more than twofold increased risk of hypoglycemia relative to nateglinide/metformin," the investigators report in the September issue of Diabetes Care.

The randomized, double-masked study compared the safety and efficacy of the two combination regimens in 428 drug-naive type 2 diabetic patients whose HbA1c ranged between 7% and 11%.

Patients received 120 mg nateglinide before three meals or 1.25 mg glyburide before breakfast, with 500 mg open-label metformin before dinner for the first 4 weeks.

This was followed by a 12-week titration period, during which glyburide and metformin were increased, if biweekly fasting plasma glucose (FPG) reached or exceeded 6.7 mmol/L, by 1.25-mg and 500-mg increments to maximum daily doses of 10 and 2,000 mg, respectively. Nateglinide was not titrated. An 88-week monitoring period followed the titration period.
Patients in both treatment arms had similar statistically and clinically significant reductions in hemoglobin A1c "very early on in the study, and essentially they were maintained over the 2-year study period. After 2 years, "it was a statistical dead heat with respect to reduction in hemoglobin A1c," stated Dr. Baron of New Jersey-based Novartis Pharmaceuticals, maker of nateglinide and study sponsor.

Specifically, in the nateglinide/metformin arm, mean A1C was 8.4% at baseline and 6.9% at week 104, while in the glyburide/metformin arm the corresponding figures were 8.3% and 6.8%.

Sixty-nine percent of patients in the nateglinide arm and 75% of those in the glyburide arm achieved a target hemoglobin A1c of less than 7%.

"It is interesting to note," Dr. Baron and colleagues write, "that when combined with metformin, essentially equivalent efficacy was achieved with an agent targeting primarily postprandial glucose and an agent that targets primarily fasting plasma glucose, highlighting the importance of the postprandial period in overall glycemic exposure."

The main difference with the two regimens was the higher incidence of hypoglycemia — and in some cases more severe hypoglycemia — with the glyburide-containing regimen. Hypoglycemia occurred in 17.7% of those receiving glyburide/metformin versus 8.2% of those receiving nateglinide/metformin.

"The difference in mechanism of action of nateglinide (a rapid-onset insulinotropic agent whose effect subsides as glucose levels fall) and glyburide (a long-acting agent that raises insulin levels throughout the day) appears to underlie the substantially improved safety profile of nateglinide/metformin in terms of hypoglycemia," the investigators say.

Summing up, Dr. Baron said that nowadays "we appreciate the fact that hyperglycemia is associated with cardiovascular risks and with certain complications and the goal is to get patients as close to normal as possible. One thing that has prohibited patients getting really close to that normal range has been the risk of hypoglycemia."

Diabetes Care. 2005;28:2093-2099

================================

DID YOU KNOW:
The Benefits of Exercise Even Without Diet: A recent study published in Diabetes Care (2005) investigated the health benefits of following a resistance-training program for 16 weeks, twice a week in Type 2 Diabetic men without following a weight loss diet. In 16 weeks, the men in the study showed improvements in their body’s response to insulin, the resting sugar levels and their total abdominal health. What is important to note is that the favorable changes in the men’s health occurred without modifying their diet, proving that exercise is an extremely powerful health modulator when completed in regular intervals. Modifying the diets of the participants with a larger quantity of fruits, vegetables, whole grains and lean protein would have probably contributed to weight loss and even further gains in health.