Last month I had a chance to chat with Vivian A. Fonseca, MD, FRCP, Tulane University Medical Center, about the GLP-1 analogs….
When asked about the use of these new drugs, in type 2 patients and why they might be better than others, Dr. Fonseca replied, “Analogs of glucagon-like peptide-1 (GLP-1) offer certain advantages in the treatment of type 2 diabetes, the most important of which is significant weight loss in the setting of improved glycemic control. Two agents in this class — exenatide and liraglutide — are currently available, and several others are in clinical trials including a once weekly injection that will certainly make management easier.”
Using Insulin or GLP-1 Analogs
We talked about the choice of using Insulin or GLP-1 analogs and Dr. Fonseca felt that there has been much debate about the best choice for patients whose control has been poor on oral agents. “Most trials have focused on a comparison between the two treatments and have reiterated the potential for weight loss with GLP-1 analogs while also demonstrating the capability of basal insulin to offer a flexible dosing schedule with the ability to lower glucose substantially, so the choice can be made for either case.”
However, I mentioned that in clinical practice, many patients have progressed to a point where they remain uncontrolled on insulin and have also gained weight, and many clinicians wonder if they can be used together.
Dr. Fonseca spoke about a multi-center parallel, randomized, placebo-controlled trial, to test whether twice-daily exenatide injections reduce hemoglobin A1c (HbA1c) levels more than placebo in people receiving insulin glargine. Adults with type 2 diabetes and HbA1c levels of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents) were randomized to receive exenatide 10 µg twice daily and insulin or placebo and insulin for 30 weeks.
According to the data he shared, the HbA1c levels decreased by 1.74% with exenatide and 1.04% with placebo:
- Weight decreased by 1.8 kg with the exenatide/ insulin combo and increased by 1.0 kg with placebo/ insulin combo.
- Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d, respectively.
- The estimated rate of minor hypoglycemia was similar between groups.
“Overall it is clear that adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine at the same time. Adverse events with exenatide included nausea, diarrhea, vomiting, headache, and constipation.”
Potential Use of Insulin and Glargine in Combination
As far as what he thinks about the use of insulin and glargine, Dr. Fonseca summed it up this way, “Currently, GLP-1 analogs are not approved in combination with insulin by the FDA. This is probably because there has not been any large study of such a combination. But does every combination of treatments need separate trials and approvals?”
“There are theoretical reasons to use such a combination. Apart from the advantages of weight loss, the incretin system plays an important role in regulating post-prandial glucose through control of gastric emptying, restoring alpha-cell function, and suppressing glucagon secretion and hopefully now that the benefits have been confirmed in a randomized trial we can use it with confidence once approved, and hope that the FDA will approve the combination soon.”