Weekly Insulin is Close to Becoming a Reality

Patients receiving weekly insulin had fewer hypoglycemic events in a new study

With Marc-André Cornier MD

Insulin and lancet

Daily injections of insulin for patients with type 2 diabetes are one of the most common reasons patients give for not adhering to their treatment regimen or discontinuation of therapy. Nearly three-quarters of patients responding to a survey noted that issues related to injections were their main reason for stopping insulin use. Given that, making those injections less frequent could be viewed as a boon to the population who may hate needles. In just a few short years, there may be weekly basal insulin injections available, removing a barrier to compliance that can have health-threatening effects on patients.

A study presented at the April ENDO-2021 endocrinology conference investigated a long-acting basal insulin formula used in comparison to a regular daily insulin. In the 32-week phase 2 study, 399 patients were randomized into three treatment groups: one of two groups getting the weekly insulin but at different doses to achieve two different goals – 120 or 140 mg/dl fasting glucose – or a group that used regular daily basal insulin. The goal for the latter was 100 mg/dl.

The weekly insulin arms had fewer hypoglycemic events, and serious events were “balanced across the three treatment groups,” as noted by the study authors. The weekly dosing groups also had smaller increases in body weight than the daily shots.

In terms of change from baseline to week 32 of HbA1c, the weekly dosing was found “non-inferior” with a mean reduction of 0.6% in A1c, compared to 0.7% in the daily insulin arm.

The results are good enough in terms of safety and tolerability to allow study of lower glucose targets, as well as study of the weekly option for patients with type 1 diabetes and other populations of patients with type 2 diabetes, the authors conclude.

The drug in the above study – basal insulin Fc (BIF) produced by Eli Lily – is one of a number of weekly insulins being investigated.

 A 26-week phase 2 study funded by Novo Nordisk looked at 247 patients randomized to take either the weekly investigational drug icodec, or a daily dose of glargine. Baseline A1c levels were 8.09% in the weekly group and 7.96% in the daily group. The former decreased by 1.33 percent over the course of the study, compared to 1.15% in the daily group. Like the above study, there was minimal difference in adverse events, and the drug and its administration were well-tolerated.

However, there are still issues of concern, according to an editorial that accompanied the study. Its authors noted that because there are so many new diabetes treatments available, the population in the study above may not be truly representative of a typical patient. They also noted that for patients who want to incorporate more exercise into their lives, the weekly dosing may not be appropriate.

Now that there have been several large clinical trials that have shown weekly insulin use to be both safe and effective – and there are still more studies of the treatment under way or planned – it could be just another couple of years before the treatment is on the market, says Marc-André Cornier MD, an endocrinologist and professor of medicine at the University of Colorado School of Medicine. FDA approval alone takes about 9 months, and it’s not clear whether any of the companies have yet submitted their work to the organization for approval.

While Cornier notes that there are other weekly medications currently used to treat type 2 diabetes and at least three weekly GLP1 receptor analogs are currently available in the United States, he thinks that eventually, the weekly treatments will be used together, possibly even combined into a single injection. “They have done this with daily medications already,” he says. “This really is a game changer.”

He sees its potential for patients with type 1 diabetes as more debatable. It is being studied, with several studies completed. Two using the Novo Nordisk drug ended phase 1 in June 2020 and December 2019. For children in particular, the idea of a weekly injection versus a daily one may be appealing – to child and parent alike. Basal insulin doses for type 1 patients rarely change much, Cornier says. “But you would have to be very careful. The potential of hypoglycemia can be catastrophic.”

Basal insulin levels are generally more stable for patients with type 2 diabetes. For them, the biggest concern is you are stuck for a week and risk hypoglycemia if the dose is too high. But generally speaking, “Basal insulin needs won’t change if your diet changes for a couple days,” according to Cornier.

That is not the case if a patient drastically changes their diet and exercise habits and loses significant weight. “If that happens, your needs will drop significantly, and that is potentially a problem,” he continues.

One concern Cornier has is that with current basal insulin, providers are taught to start low and titrate the dose up. But for many, they don’t stop increasing the dosages. “I think we really have to be more careful.”

While he is hopeful that his patients can benefit from this breakthrough in treatment in the near future, he is also cautious. There have been other “breakthroughs” that haven’t panned out. “I remember there was a company that tried to use exenatide in an implantable device that would last 6 months. But it just never moved forward. I think with insulin, there are issues with making it much longer acting. You run a greater risk of hypoglycemia the longer acting it is.”

Until something is close to being available or available, Cornier isn’t going to bring the topic up for his patients. “If you talk too much about something easier coming down the road, some patients might decide to do nothing. Why do hard if easy is around the corner? We have been burned before. Sometimes, drugs don’t make it to market.”

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