Spotlight on novel therapies for type 1 diabetes

Several recent articles examined potential new therapies for type 1 diabetes.

First, an industry trial, published by The Lancet on Oct. 17, reported the effects of weekly insulin (icodec) in adults with type 1 diabetes. Patients were randomized without blinding to icodec (n=290) or daily insulin degludec (n=292). At 26 weeks, the estimated mean change in HbA1c level was −0.47 percentage point versus −0.51 percentage point, respectively, showing icodec to be noninferior. However, at the same time point, the overall rate of clinically significant or severe hypoglycemia was higher with icodec than degludec (19.9 vs. 10.4 events per patient-year of exposure; P<0.0001). The study authors noted that the trial met its primary objective of showing a similar decrease in HbA1c level as daily insulin and that the rate of hypoglycemia with icodec could potentially be improved with dose adjustments. They did caution that the included patients had good glycemic control and self-management skills, which could affect generalizability. “Given the nature of type 1 diabetes, switching individuals from daily basal insulin injections to a once-weekly basal insulin is likely to be challenging,” the authors said. They called for real-world studies to determine if weekly insulin works well for patients with type 1 diabetes who struggle with adherence to daily insulin injections.

A phase 3 manufacturer trial, published by the New England Journal of Medicine on Oct. 18, tested teplizumab, a humanized monoclonal antibody to CD3 on T cells, in children recently diagnosed with type 1 diabetes. (The drug is already FDA approved to delay the onset of clinical type 1 diabetes.) The study found that patients randomized to two 12-day courses of teplizumab (n=217) had significantly higher stimulated C-peptide levels than those given placebo (n=111). Significantly more also maintained a clinically meaningful peak C-peptide level, but the groups did not differ significantly on insulin use, HbA1c levels, time in target range, or hypoglycemic events. The study authors noted that the trial was probably underpowered to address these secondary end points.

A meta-analysis, published by The Lancet Diabetes & Endocrinology on Nov. 3, looked more broadly at disease-modifying therapies to prevent beta-cell loss in recent-onset type 1 diabetes. It included 21 trials testing such interventions in 1,315 adults and 1,396 children and found that in positive studies, at six months, a 24.8% increase in C-peptide preservation was associated with a 0.55% lower HbA1c level (P<0.0001). Differences were detectable as early as three months. According to the review authors, the findings show “that successful disease-modifying therapy resulting in C-peptide preservation improves metabolic outcomes in type 1 diabetes, notably glycaemic control as measured by HbA1c,” which supports “consideration of an alternative approach to address this, focussing on treatment of the disease (autoimmune destruction of β cells), rather than relying on insulin to treat the resulting disability (insulin deficiency).” The authors also suggest their data supports “the use of C-peptide as a surrogate endpoint in clinical trials.” An accompanying editorial called those conclusions “very optimistic” and pointed out that “so far no intervention has turned out to increase endogenous insulin secretion in patients with recent-onset type 1 diabetes on the group level.”

Finally, a review, published by Diabetologia on Oct. 6, analyzed the potential of newer type 2 therapeutics to also prevent and treat chronic kidney disease in type 1 diabetes. It discussed how sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists could offer some of the same benefits in type 1 diabetes that they have proven to provide in type 2. “Regrettably, people with type 1 diabetes have not been able to benefit from this expanded armamentarium of therapeutic agents and remain at unacceptably high risk of kidney and cardiovascular complications. The translation of these and other novel therapies … requires a concerted demonstration of efficacy and safety in dedicated and properly designed cardiorenal outcome trials,” the review concluded.