The therapeutic combination of insulin degludec with liraglutide (a long-acting glucagon-like peptide-1 receptor agonist that stimulates insulin secretion) was approved in September 2014 as a new therapeutic for adults with type 2 diabetes. The treatment is prescribed for adults who, despite other treatments, still present high levels of glucose in their blood.
The German Institute for Quality and Efficiency in Health Care (IQWiG), a public health organization responsible for investigating the benefits and risks of medical interventions for patients, revised the effects of the drug combination to assess its added therapeutic value in relation to its comparator therapy.
The Federal Joint Committee (G-BA), the highest decision-making body of the joint self-government of physicians, dentists, hospitals and health insurance funds in Germany, distinguished two treatment scenarios for the therapeutic combination of insulin degludec with liraglutide — type 2 diabetes patients use it together with other oral antidiabetics when (1) oral therapy with several oral antidiabetics or (2) with oral antidiabetics together with basal insulin fail to control blood glucose levels.
The G-BA determined that the first parameter — oral therapy with several oral antidiabetics — was incorrectly investigated by the manufacturer, since it only performed a randomized controlled trial with patients receiving only one oral antidiabetics drug (metformin) in monotherapy. Additionally, the control population did not receive the appropriate comparator therapy, as specified by the G-BA (control subjects were given an analogue, insulin degludec, and not human insulin).
Because of this, the G-BA concluded that, since the manufacturer did not confirm that indeed insulin degludec effects are comparable to human insulin, the latter couldn’t be used as a comparator therapy in the study.
The G-BA found that the second parameter — oral antidiabetics together with basal insulin — also failed to comply with their guidelines: incorrect use of comparator therapy and liraglutide administration only in the intervention group but not in the comparator arm. Additionally, the G-BA guidelines stipulate that, within a period of three to six months, if desirable target blood glucose levels fail therapeutic strategy must change. Basal insulin (the strategy chosen) was continued and small adjustments were implemented but only in the comparator arm (leading to biased interpretations).
Because studies performed showed procedural errors, the G-BA concluded that no conclusions can be obtained concerning the added benefit of insulin degludec with liraglutide in treating type 2 diabetes.