Combining Insulin and Amylin to Treat Type 1 Diabetes

Maintaining blood sugar levels in range after meals is probably one of the toughest challenges that people with type 1 diabetes (T1D) have to face. Other than taking into account the countless, non-meal related factors that can impact blood sugar levels, they have to count the exact number of carbs they’re eating and anticipate how their meal will impact their blood sugar.

Managing post-meal blood sugar levels remains a challenge, despite the arrival of new technologies (e.g., continuous glucose monitoring [CGM] systems, hybrid closed loop systems) and new types of insulin (e.g., Fiasp) on the market.

Amylin: A hormone that helps to manage blood sugar levels around meals  

Healthy pancreas beta cells secrete insulin and amylin, two hormones that work together to manage post-meal blood sugar levels. By slowing down the emptying of the stomach and boosting the feeling of fullness, amylin delays the entry of glucose into the bloodstream and, consequently, the blood sugar increase.  

In people with T1D, pancreas beta cells have been destroyed by antibodies, which prevents the natural secretion of insulin and amylin. While insulin can be administered with pens, syringes or insulin pumps, there is still no successful treatment to substitute the missing amylin for people with T1D.

Pramlintide treatment: An injectable amylin substitute 

An injectable synthetic analog of human amylin has been available in the U.S. since 2005. Although pramlintide (SymlinⓇ) has proven beneficial for people with T1D (e.g., improved post-meal blood sugar levels, improved glycated hemoglobin, reduced boluses, weight loss), it wasn’t authorized in a number of countries, including Canada, due to the increased risk of hypoglycemia and certain digestive side effects (e.g., nausea) observed in studies.

There aren’t many takers for this treatment in the U.S.; people with T1D are not too keen on taking additional injections at mealtimes or forking out a large sum of money.

A new treatment under review 

A new treatment aimed at improving post-meal blood sugar levels is currently under review. The ADO09 treatment combines pramlintide and rapid-acting insulin in the same vial. A study published in January 2023 compared treatment with AD009 to treatment with rapid-acting insulin only, and described how combining insulin and pramlintide could benefit people with T1D.

The results showed that the AD009 treatment could not only improve post-meal blood sugar and average blood sugar levels, but also significantly increase time spent in range, regardless of the number of units of insulin required daily. Moreover, AD009 also helped to achieve modest weight loss (-1.64 kg) compared to rapid-acting insulin only (+0.37 kg), and positively impacted satiety (the feeling of fullness) for almost all participants.  

No severe hypoglycemic episodes were reported during the study. Although the number of hypoglycemic episodes was slightly higher with AD009, the total time spent in hypoglycemia, as calculated by a CGM, wasn’t higher with AD009 than with rapid-acting insulin only. Light gastrointestinal side effects such as nausea were reported, mostly at the start of treatment.

Can both hormones be combined for use in an artificial pancreas?

Researchers at McGill University in Montreal were the first to experiment the use of pramlintide in an artificial pancreas system.

In a study published in 2020, they showed that adding pramlintide to rapid-acting insulin in an artificial pancreas system improves glycemic control compared to treatment with rapid-acting insulin only and doesn’t increase the risk of hypoglycemia. 

The research team is currently leading a new clinical trial to see whether using a combination of insulin and pramlintide in an artificial pancreas could facilitate—or even eliminate—carb counting for teens and adults with T1D. 

There are many initiatives aiming to make insulin more effective and easier to use by combining it with other products. The insulin/pramlintide trials could be a first step towards facilitating post-meal blood sugar management.

References :

• Whitehouse, Fred et al. “A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes.” Diabetes care vol. 25,4 (2002): 724-30. doi:10.2337/diacare.25.4.724
• Ratner, R E et al. “Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial.” Diabetic medicine : a journal of the British Diabetic Association vol. 21,11 (2004): 1204-12. doi:10.1111/j.1464-5491.2004.01319.x
• Andersen, Grit et al. “A co-formulation of pramlintide and insulin A21G (ADO09) improves post-prandial glucose and short-term control of mean glucose, time in range, and body weight versus insulin aspart in adults with type 1 diabetes.” Diabetes, obesity & metabolism, 10.1111/dom.14972. 12 Jan. 2023, doi:10.1111/dom.14972
• Andersen G, Meiffren G, Famulla S, Heise T, Ranson A, Seroussi C, et al. ADO09, a coformulation of the amylin analogue pramlintide and the insulin analogue A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes. Diabetes Obes Metab. 2021;23(4):961-70.
• Haidar, Ahmad et al. “A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial.” Diabetes care vol. 43,3 (2020): 597-606. doi:10.2337/dc19-1922