Are Weekly Insulin Injections Set to Transform Diabetes Treatment?

Both Novo Nordisk and Eli Lilly are leading the diabetes space with several insulin types. Although more attention has been paid to GLPs anti-obesity drugs, both the companies continue to invest in diabetes to get more options.

• The competition in the insulin market is becoming more dynamic as Lilly announced positive Phase III trial topline results for its weekly insulin injection, efsitora (in insulin-naive adults with T2D and those who require multiple daily insulin injections). The readouts tick off two of the five upcoming efsitora R&D milestones. Lilly is expected to present detail results at upcoming EASD Sept’024.
• These results come just a few days before the once-weekly, Novo’s insulin icodec (Awiqli), will be discussed by the USFDA Adcom scheduled May 24th. Awiqli already received positive CHMP opinion for EU approval. EC approval is expected in Q2’2024 itself. If approved, this would make Novo the first to offer basal insulin on a weekly basis. While Novo’s progression of its once-weekly insulin has been overshadowed by impressive weight loss data from its oral amycretin and semaglutide’s market success, Novo is also doing a trial of icodec with its GLP-1 semaglutide.

A weekly insulin has the potential to be transformational and likely will change the landscape of diabetes management- they are reducing the number of injections per year from 365 to 52. Both Awiqli and efsitora have been associated with higher patient satisfaction compared to daily insulin regimens, primarily due to the convenience of weekly injections. This should, conceivably, improve treatment adherence, ultimately leading to improved glycaemic control.

Injecting insulin is a burden to remember every day and not having to inject daily could be seen as a benefit. However, It might be harder to develop the habit and to remember an injection that only happens 1 time a week. Other potential challenges could be-

• Dosing Flexibility: Weekly injections offer less flexibility to adjust doses in response to short-term changes in blood sugar levels, diet, or physical activity. Basal insulin needs may not be static in growing children, menstruating women, teens or athletes. Insulin sensitivity quickly changes as a result of exercise, stress, or hormones to name a few of the factors. The inability to adjust insulin for a week could be concerning.
• Consequences of Missed Doses: Missing a weekly dose can lead to more significant and potentially severe consequences compared to missing a daily dose.

• Hypoglycemia: The possible risk for hypoglycemia with long-acting insulin, particularly in patients with variable schedules. Hypoglycemia might occur with sporadic exercise or with skipped meals but in general should not be a major issue.?It should be great for some patients where hypoglycemia is less of a concern, and they're in a more stable environment. Further studies evaluating these issues (e.g., exercise) should help.
• Adjustment Period: Patients might need time to adapt to the new regimen, and there could be initial instability in glucose control during the transition.
• Pricing: There could be a higher upfront cost for weekly injections but given political pressure and new Medicaid and Medicare laws could lower these costs more than expected. Both Lilly and Novo, as well as Sanofi, have been in the spotlight for their pricing of currently marketed insulin products. Last year, in response to sustained political pressure, all three lowered the list prices of their on-market insulins. The move coincided with recent changes in law that eliminated a cap on rebates paid into Medicaid, as well as placed a $35 monthly cap on OOP costs for insulin in Medicare. The companies had been paying substantial rebates to insurers for their insulin products, meaning that net prices of the drugs were substantially lower than their list price.
• Affordability: Insurance plans may not cover them initially, especially given that the data thus far show noninferiority, not superiority, to daily basal. For low-income group, these may not be affordable for those who could most benefit from them in terms of improved adherence.
• Long-Term Data: As newer therapies, there is less long-term safety and efficacy data compared to well-established daily insulins.

A majority of these issues may not be concerning and can be potentially address via a good patient support programs.

Overall, weekly insulin injections like Awiqli and efsitora should offer a promising alternative to daily injections, with potential benefits in convenience and adherence, balanced by the need for careful patient education and monitoring.

Sources referred: The Lancet; NEJM; ADA; EASD; Diabetes Care; Fierce Biotech

#insulins #T2D #diabetescare #pharmaindustry #diabetesmanagement #metabolicdisorders #obesity