How common is severe hypoglycaemia with Insulin? Grade A evidence

What the studies show

The defining harm. Intensive therapy in the DCCT roughly tripled severe hypoglycaemia; in UKPDS the rate of major episodes on insulin was 1.8% a year against 0.7% on conventional treatment.

“The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.”

Verbatim, from the abstractThe Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med, 1993;329:977–986

Several well-run randomised trials in people, pointing the same way. You can plan around this. It still says nothing about whether the effect is worth the side effects for you.

1
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N Engl J Med, 1993;329:977–9861,441 patients, mean 6.5 years.
2
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).Lancet, 1998;352:837–8533,867 newly diagnosed patients, 10 years.

In context

Insulin is the 51-amino-acid hormone that lets cells take up glucose; recombinant human insulin and its engineered analogues are the treatment for type 1 diabetes and a mainstay of type 2. The landmark trials are settled: intensive insulin therapy cut new diabetic eye disease by 76% over six and a half years in the DCCT, and intensive glucose control reduced microvascular complications by a quarter over ten years in UKPDS. The cost, quantified in the same trials, is severe hypoglycaemia. It is on this site as the reference peptide, and because it is on WADA's list.

Insulin is approved (rx). Legal status differs by country — see the regulation section or the jurisdiction pages.

Questions

Is Insulin proven to cause severe hypoglycaemia?

Yes, as far as human trials can show it: Both landmark RCTs. LYO grades this outcome A.

What studies are behind the grade?

The defining harm. Intensive therapy in the DCCT roughly tripled severe hypoglycaemia; in UKPDS the rate of major episodes on insulin was 1.8% a year against 0.7% on conventional treatment.

Is Insulin approved for this?

Insulin is an approved medicine (Approved (Rx)); whether this particular outcome is a licensed indication is stated on the compound page's regulation section.

Other outcomes for Insulin

ADiabetic retinopathy (type 1, intensive vs conventional)1 large RCT (DCCT, n=1,441, 6.5 yr)
AMicrovascular complications (type 2)1 large RCT (UKPDS 33, n=3,867, 10 yr)
AWeight gainadverseUKPDS and many

Written and maintained by LYO Research — how pages are written and checked. Reviewed 7 October 2026. Grades count human evidence only; see how LYO grades. Not medical advice. Correct this page →