ADA: Diabetes Patients Shed Pounds with Insulin Analog

Julio Rosenstock, MD, of Dallas Diabetes and Endocrine Center, and colleagues reported during a poster session, that in two separate phase II studies, patients with both type 1 and type 2 diabetes shed pounds on the novel insulin, although the effect was greater in patients with type 1 disease. 

Researchers conducted two phase II trials of the once-daily insulin analog: one in 288 patients with type 2 diabetes over 12 weeks, and another in 137 patients with type 2 diabetes who were treated for 8 weeks.

In both studies, the drug, a PEGylated insulin lispro that has altered absorption and reduced clearance associated with a large hydrodynamic size, was associated with comparable or better glycemic control than insulin glargine (Lantus) as well as weight loss.

For type 1 diabetics, the improvements in glycated hemoglobin (HbA1c) with the novel insulin were significantly better than those seen with insulin glargine (-0.6% versus -0.4%, P<0.05).

Patients on the investigational agent lost a mean of 2.65 lbs., while those on insulin glargine gained a mean of 1.52 lbs. (P<0.001), and significantly more patients on the novel insulin lost 5% of their body weight (12% versus 1%, P<0.001).

The weight loss mechanism was unclear because the novel insulin patients had higher rates of gastrointestinal effects, including nausea, abdominal distention, and dyspepsia (15% versus 4% overall). Yet the researchers said that patients who lost more weight were less likely to have gastrointestinal effects, leaving.

They also noted that the investigational drug carried a higher risk of hypoglycemia (8.7 events versus 7.4 events per month, P=0.04) but a lower risk of nocturnal hypoglycemia (0.9 versus 1.1 events, P=0.01).

For patients with type 2 diabetes, the novel drug provided similar improvements in glycemic control as insulin glargine. It also provided a mean weight loss of 1.28 lbs., compared with a gain of 0.68 lbs. for those on insulin glargine (P<0.01), and more patients on the investigational agent lost 5% of their body weight (5% versus 0%, P=0.03). These patients also had more GI effects, but it wasn't a significant difference from GI events in those on insulin glargine (14% versus 10%).

Overall hypoglycemia rates were similar between the two agents, but those on the novel drug had less nocturnal hypoglycemia, the researchers said.

Mel Prince, MD, senior medical director at Eli Lilly, mentioned that, "It wasn't a consistent finding in both trials and these are small, phase II trials," adding that the type 2 study was larger and longer, and the effect on weight loss wasn't as strong.

Prince said the effect likely has something to do with the fact that the new insulin acts more in the liver than other insulins, which enables the patient to ultimately break down more fat because insulin in the periphery tends to inhibit the breakdown of fat in adipocytes.

He cautioned, however, that the hypothesis is based on preclinical findings and that he doesn't expect it to show up in larger trials.

• Note that in this study, the PEGylated insulin lispro, which has altered absorption and reduced clearance associated with a large hydrodynamic size, was associated with comparable or better glycemic control than insulin glargine as well as reduced weight.
• These studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. 

Jacober SJ, et al "Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycemic control in T1D and T2D" ADA 2012; Abstract 1023-P. Rosenstock J, et al "Better glycemic control and weight loss with novel long-acting basal insulin LY2605541 compared with insulin glargine in patients with type 1 diabetes" ADA 2012; Abstract 1026-P.