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“smart” insulin 

Peng Liu

Biggest medical discoveries

Researchers have developed a novel “smart” insulin called NNC2215 that shows promise in addressing one of the major challenges of insulin therapy for diabetes: the risk of hypoglycemia (dangerously low blood sugar)[1][2].

How NNC2215 Works

NNC2215 is an insulin molecule engineered with a glucose-sensitive switch consisting of two key components:

  1. A ring-shaped macrocycle structure
  2. A glucoside molecule derived from glucose

This innovative design allows NNC2215 to automatically adjust its activity based on blood glucose levels:

  • When glucose is low, the glucoside binds to the ring, keeping insulin inactive
  • As glucose rises, it displaces the glucoside, activating the insulin[3]

Key Advantages

Glucose-Responsive Action: NNC2215 can turn its activity on and off in response to changing blood sugar levels, unlike traditional insulin[3].

Hypoglycemia Prevention: In animal studies, NNC2215 demonstrated the ability to lower high blood glucose effectively while preventing the dangerous drops in blood sugar that can occur with regular insulin treatment[1][2].

Reversible Effect: Unlike some previous glucose-sensitive insulin approaches that irreversibly release insulin, NNC2215’s activity can be reined in when glucose levels fall[3].

Research Findings

Studies in pigs and diabetic rats showed that:

  • NNC2215 was as effective as human insulin in lowering blood glucose
  • It provided protection against hypoglycemia compared to a current long-acting insulin (insulin degludec)
  • During a glucose challenge, NNC2215 activation corresponded to the effect of about 30% additional human insulin[1]

In one experiment, when glucose infusion was stopped:

  • NNC2215 allowed glucose to drop to about 4.5 mM
  • Insulin degludec caused a drop to about 3 mM (hypoglycemic range)[1]

Potential Impact

This glucose-sensitive insulin could significantly improve diabetes management by:

  1. Reducing the risk of hypoglycemic events
  2. Improving quality of life for people with diabetes
  3. Potentially allowing for more aggressive glucose control with less fear of low blood sugar[2][3]

While further research is needed to optimize NNC2215 and assess its safety and efficacy in humans, this development represents a promising step toward more automated and safer insulin therapy for diabetes.

Citations:
[1] https://assets-eu.researchsquare.com/files/rs-2882397/v1/1e7e4dfd-92d3-4b6e-b79d-451074f743b0.pdf?c=1729149088
[2] https://www.nature.com/articles/s41586-024-08042-3
[3] https://www.nature.com/articles/d41586-024-03357-7
[4] https://www.news-medical.net/news/20241018/New-glucose-sensitive-insulin-NNC2215-could-transform-diabetes-care-by-lowering-hypoglycemia-risk.aspx
[5] https://pubmed.ncbi.nlm.nih.gov/39415004/?fc=None&ff=20241018054337&v=2.18.0.post9+e462414
[6] https://www.researchgate.net/publication/370676441_Glucose-sensitive_insulin_with_attenuation_of_hypoglycaemia
[7] https://twitter.com/MoEbrahimkhani/status/1846618934830944543
[8] https://twitter.com/DanielJDrucker/status/1846588322551902458