of the major advantages of linagliptin is that it works in a blood
glucose-dependent manner, i.e. it releases insulin from the pancreas when the
blood sugar is high and insulin is needed. On the other hand, sulfonylureas
(glimepiride) release insulin from the pancreas independent of blood sugar
level. Therefore, using sulfonylureas exposes the patients to risks of
The clinical trial was conducted at 209 sites,
across 16 countries, for 104 weeks in type 2 diabetes patients aged 18-80
years. The enrolled patients were receiving ≥1500 mg/day metformin with
another oral anti-diabetic drug such as
5 mg linagliptin
(777 patients) or 1-4 mg glimepiride
(775 patients) once-a-day
. The alterations in glycated hemoglobin A1c (HbA1c)
levels were the primary endpoint
, measured from
baseline to week 104.
in average HbA1c was comparable
in linagliptin (-0·16%) and glimepiride
groups (-0·36%), but the overall incidence of any drug-related adverse
events was lower in patients treated with linagliptin.Fewer linagliptin-treated patients had hypoglycaemia (7%) and cardiac
episodes (12) as compared with glimepiride-treated patients (36% and 26).
Severe hypoglycemia was reported in 1 linagliptin patient as compared to 12
glimepiride patients. Weight gain reduced in the linagliptin group (-1·4 kg)
but rose in glimepiride group (1·3 kg).
Thus linagliptin is as efficacious as, but
safer than, glimepiride as a treatment choice for type 2 diabetes mellitus
patients for whom metformin monotherapy is inadequate. The linagliptin plus
metformin combination therapy should be considered in type 2 diabetes treatment.
2-year efficacy and safety of
linagliptin compared with glimepiride in patients with type 2 diabetes
inadequately controlled on metformin: a randomized, double-blind,
non-inferiority trial; Baptist Gallwitz et al; The Lancet Online Publication