Peglispro allows slow insulin absorption, but associated with injection site reaction and increased ALT and triglycerides…
Peglispro or pegylated lispro insulin is currently under phase III investigation for both type 1 and type 2 diabetes. The large hydrodynamic size of peglispro allows slow insulin absorption and reduces clearance, resulting in prolonged duration of action.
It also has reduced peripheral effects thus resulting in a hepato-preferential action more like endogenous insulin. Several studies have been conducted to evaluate the effects of peglispro in A1c reduction, nocturnal hypoglycemia, and changes in lipid panels.
The results from three double-blind, randomized clinical trials showed that peglispro (BIL) is superior to insulin glargine (GL) in A1c reduction in both type 1 and type 2 diabetes. In one of the studies, BIL was compared to GL in insulin-naïve type 2 diabetes patients treated with oral antihyperglycemic medication. The researchers found that BIL patients had lower HbA1c (6.9 vs. 7.2%, p < .001) and more had HbA1c < 7% (58 vs. 43%, p < .001) after 52 weeks of treatment. Furthermore, weight gain was less with the BIL group compared to GL group while the total hypoglycemia rates were similar in both groups.
When BIL is compared to GL in type 1 diabetes patients, A1c reductions were also greater in the BIL treated group versus GL group at week 26 with treatment difference -0.37%; 95% CI: -0.50,-0.23. However, the rate for hypoglycemia was higher for the BIL group. In another study, comparing BIL with GL in type 1 diabetes patients, there was a 0.48% reduction in BIL group versus only 0.25% reduction in GL treated patients. The total hypoglycemia rate was 11% higher with BIL while the severe hypoglycemia rates were similar.
In addition, both type 1 and type 2 DM patients treated with peglispo had higher rate of reaching A1c less than 7% and experienced less nocturnal hypoglycemia. However, peglispo treatment groups were associated with injection site reaction, higher triglycerides and ALT ≥ 3x ULN.
The findings from these studies suggest the use of peglispro as an alternative basal insulin for treatment of diabetes. Despite a noticeably higher A1c reduction when compared to insulin glargine, peglispro is associated with increased triglycerides and ALT, suggesting liver toxicity as a potential side effect. Thus, further investigation and understanding of the liver issue is recommended before it can be considered as a safe and effective treatment for diabetes. On the other hand, peglispro offers better clinical advantages over insulin glargine by reducing nocturnal hypoglycemia and promoting potential weight loss. Therefore, the benefits of using peglispro might outweigh the risks in certain patients.
- Risks for hypoglycemia are often associated with the use of insulin in treatment of diabetes.
- Peglispro is a novel basal insulin and it is suggested to have a flat activity profile and prolonged duration of action.
- Peglispro is superior to insulin glargine in A1c reduction and less nocturnal hypoglycemia in both type 1 and type 2 diabetes, but associated with increased ALT and triglycerides.
Melanie j. Davies, David Russell-Jones, Jean-Louis Selam, et al. Basal Insulin Peglispro (BIL) Is Superior to Insulin Glargine (GL) in Reducing HbA1c at 52 Wks in Insulin-Naïve T2D Patients (Pts) Treated with Oral Antihyperglycemic Medications (OAMs): IMAGINE 2. American Diabetes Association 2015 Scientific Sessions; June 6, 2015; Boston, MA. Abstract 93-OR