GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients.
BACKGROUND
Progressive beta-cell failure is a characteristic feature of type 2 diabetes; consequently, beta-cell secretagogues are useful for achieving sufficient glycaemic control. The European GUIDE study is the first large-scale head-to-head comparison of two sulphonylureas designed for once-daily administration used under conditions of everyday clinical practice.


METHODS
Eight hundred and forty-five type 2 diabetic patients were randomized to either gliclazide modified release (MR) 30-120 mg daily or glimepiride 1-6 mg daily as monotherapy or in combination with their current treatment (metformin or an alpha-glucosidase inhibitor) according to a double-blind, 27-week, parallel-group design. Efficacy was evaluated by HbA1c and safety by hypoglycaemic episodes using the European Agency definition.


RESULTS
HbA1c decreased similarly in both groups from 8.4% to 7.2% on gliclazide MR and from 8.2% to 7.2% on glimepiride. Approximately 50% of the patients achieved HbA1c levels less than 7%, and 25% less than 6.5%. The mean difference between groups of the final HbA1c was -0.06% (noninferiority test P < 0.0001). No hypoglycaemia requiring external assistance occurred. Hypoglycaemia with blood glucose level < 3 mmol L(-1) occurred significantly less frequently (P = 0.003) with gliclazide MR (3.7% of patients) compared with glimepiride (8.9% of patients). The distribution of the sulphonylurea doses was similar in both groups.


CONCLUSIONS
This study provides new insights into therapeutic strategies using sulphonylureas. It shows that gliclazide MR is at least as effective as glimepiride, either as monotherapy or in combination. The safety of gliclazide MR was significantly better, demonstrating approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride.
Rudolfstiftung Hospital, Vienna, Austria. guntram.schernthaner@wienkav.at
G
G
Schernthaner
A
A
Grimaldi
U
U
Di Mario
J
J
Drzewoski
P
P
Kempler
M
M
Kvapil
A
A
Novials
R
R
Rottiers
G E H M
GE
Rutten
K M
KM
Shaw
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005907:Gliclazide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D005907:Gliclazide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride