Regardless of the degree of glycaemic control, linagliptin has lower hypoglycaemia risk than all doses of glimepiride, at all time points, over the course of a 2-year trial.
AIM
To evaluate the risk of documented hypoglycaemia with glimepiride versus linagliptin.


METHODS
This was an exploratory analysis of data from a 2-year, randomized, double-blind study of the dipeptidyl peptidase-4 inhibitor linagliptin 5 mg once daily (n = 764) versus the sulphonylurea glimepiride 1-4 mg once daily (n = 755) in patients with type 2 diabetes uncontrolled by metformin. Patients randomized to glimepiride started on 1 mg and after 4 weeks were allowed to be individually uptitrated stepwise to glimepiride 4 mg if a fasting plasma glucose concentration ≤6.1 mmol/l was not achieved. Investigator-reported hypoglycaemia was evaluated by dose, over time, and by the degree of glycated haemoglobin (HbA1c) reduction.


RESULTS
The percentages of patients with at least one hypoglycaemic event at the individual maximum glimepiride dose were: 1 mg, 45.0%; 2 mg, 50.8%; 3 mg, 36.1%; and 4 mg, 27.7%. The incidence of hypoglycaemia was higher with glimepiride than with linagliptin (36.1 vs. 7.5%; p < 0.0001); after performing sensitivity analyses by excluding events during dose escalation (weeks 0-16), this difference remained significant (weeks 16-104: 25.8 vs. 5.9%; p < 0.0001). Notably, the incidence of hypoglycaemia was higher with glimepiride than with linagliptin in each quartile of HbA1c change from baseline (all p < 0.0001); the incidence of hypoglycaemic episodes was not increased with greater reductions in HbA1c in either group. In all 4-week intervals across the 2-year study, the incidence of hypoglycaemia was lower with linagliptin than with glimepiride.


CONCLUSION
Linagliptin was associated with a lower risk of hypoglycaemia than glimepiride at all dose levels and time intervals, and regardless of change in HbA1c level.
['Gallwitz|B|B|', 'Rosenstock|J|J|', 'Patel|S|S|', 'von Eynatten|M|M|', 'Hehnke|U|U|', 'Mehlburger|L|L|', 'Dugi|K A|KA|', 'Woerle|H-J|HJ|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D001786:Blood Glucose D003924:Diabetes Mellitus, Type 2 D004311:Double-Blind Method D005260:Female D006442:Glycated Hemoglobin A D006801:Humans D007003:Hypoglycemia D007004:Hypoglycemic Agents D000069476:Linagliptin D008297:Male D008875:Middle Aged D011687:Purines D011799:Quinazolines D012306:Risk D013453:Sulfonylurea Compounds D013997:Time Factors D055815:Young Adult
glycaemic control sulphonylurea type 2 diabetes DPP-4 inhibitor incretin therapy