A yearlong clinical trial in more than a dozen countries reveals that once-a-week-Trulicity, used in conjunction with short acting insulin, not only improved blood sugar control for subjects with type 2 diabetes, but also curbed hypoglycemia compared to a standard treatment and reduced weight in trial subjects.
“This study confirmed what we expected” said Dr. Zvonko Milicevic, a researcher with Eli Lilly & Co., the company that developed the drug dulaglutide, marketed as Trulicity. “The benefits we found in this study for subjects who received Trulicity was not only improved glycemic control, but also reduced hypoglycemia and reduced weight compared to people using a standard insulin treatment.”
Trulicity is in a class of treatments known as GLP-1 receptor agonists—short for glucagon-like peptide-1 receptor agonists. GLP-1 is a hormone in the body that gets released in the intestine during the stage of digestion when carbohydrates are absorbed, stimulating the release of insulin from pancreatic beta cells. Additionally, GLP-1 is present in the brain and functions as an appetite suppressant.
Trulicity is a once-weekly injectable treatment option that was approved for use in the United States last September by the Food and Drug Administration in 0.75 mg and 1.5 mg dose. For the trial, Trulicity was compared to insulin glargine, a once-daily injectable treatment, the most popular of which is Sanofi’s Lantus. Both agents were combined with short-acting mealtime insulin lispro.
The trial tested the effectiveness of Trulicity 0.75 mg and 1.5 mg in combination with mealtime insulin, Milicevic said, by comparing it to a basal-bolus approach to insulin treatment in patients with type 2 diabetes. Basal-bolus therapy is when a diabetic takes long acting insulin once a day to stabilize glucose levels while fasting, while also taking short-acting insulin before main meals to counteract increases in blood glucose levels from eating. Basal-bolus therapy is thought by many to approximate the way in which a person without diabetes produces insulin.
According to Eli Lilly & Co., the clinical trial for Trulicity was global in scale. The trial lasted 52 weeks and was conducted at 105 study sites in 15 countries. Most of the trial’s 884 patients were from the United States, while others were from Europe, South America, and Asia.
Lilly said that after 26 weeks on once-weekly Trulicity subjects saw a reduction in their baseline A1c levels of between 1.59 and 1.64 percent (depending on the dosage). The A1c levels of subjects taking once-daily Lantus were reduced by 1.41 percent.
Trulicity also delivered two additional improvements for type 2 diabetics, Milicevic said.
“We saw a reduction in hypoglycemic episodes,” said Milicevic, who began his career in diabetes 30 years ago by becoming involved in work related to hypoglycemia. “There were approximately 20 percent fewer hypoglycemic events with Trulicity 1.5 mg, compared to glargine, and there were fewer severe events.”
By hypoglycemia he meant a blood sugar reading of 70 or less, or signs and symptoms of low blood sugar, or both. For severe events he meant episodes that required help from another person to resolve.
Milicevic said there were almost 40,000 hypoglycemic events in the study. “Hypoglycemia is an important problem for type 2 diabetics who take insulin,” said Milicevic. “So a 20 percent reduction is a significant improvement.”
Milicevic estimated that 20 to 30 percent of all type 2 diabetics are currently being treated with insulin, while the other 70 to 80 percent take oral medications to stabilize their blood sugar.
The other improvement was in weight.
According to Lilly, during the course of the trial subjects who received Trulicity 1.5 mg lost an average of 0.87 kg after 26 weeks and 0.35 kg after 52 weeks. Subjects who took Lantus gained 2.33 kg on average after 26 weeks and 2.89 kg after 52 weeks.
“While this might not sound like a considerable amount of weight, it can represent a significant difference for a person with diabetes,” Milicevic said.
Subjects using Trulicity reported they experienced some gastrointestinal side effects more commonly than those using Lantus. Between 16 and 17 percent of subjects on Trulicity (depending on the dose) experienced diarrhea, while between 18 and 26 percent suffered from nausea. By contrast, 6 percent of subjects on Lantus experienced diarrhea and 3 percent of subjects reported nausea. Those results are similar to earlier clinical trials for Trulicity.
While the results from the study were mostly positive for Trulicity, there is one major obstacle to more widespread use of GLP-1s that is affecting all such treatments, whether they are administered daily or weekly.
“The general position is that convincing people with type 2 diabetes to use any injectable therapy rather than an oral agent is a significant barrier to the success of those therapies,” Milicevic said. “I hope that the reduction in A1c, plus the reduction in hypoglycemic events and weight loss in the subjects enrolled in this trial will help us overcome that barrier.”