Sulphonylurea monotherapy for patients with type 2 diabetes mellitus

Monotherapy with second generation sulphonylureas (glibenclamide or glyburide, glibornuride, gliclazide, glipizide) appears to be associated with a higher risk of severe hypoglycaemia than treatment with other oral antidiabetic drugs in patients with type 2 DM. Compared to metformin, sulphonylurea monotherapy may be equally effective in reducing fasting blood sugar and HbA1c, and may result in less macrovascular complications.

The quality of evidence is downgraded by imprecision (few events).

The recommendation attaches a relatively high value on avoiding adverse effects caused by hypoglycaemia.

Summary

A Cochrane review [withdrawn from publication] included 72 RCTs with a total of 22,589 participants comparing the effects of sulphonylurea monotherapy versus placebo, no intervention or other antidiabetic interventions for patients with type 2 diabetes mellitus (T2DM). The patients were 18 years old or more (mean age 40.3 to 74.4 years) and the duration of the interventions varied from 24 weeks to 10.7 years. None of the included trials was assessed as low risk of bias for all bias domains.

The effects of second-generation sulphonylureas on patient-important outcomes compared to metformin or insulin are given in table 1.

With second-generation sulphonylureas (glibenclamide or glyburide, glibornuride, gliclazide, glipizide) change in fasting blood glucose was significantly lower compared to metformin (random MD 0.43 mmol/L, 95% CI 0.10 to 0.75; fixed MD 0.42 mmol/L, 95% CI 0.28 to 0.56; n = 3891, 11 trials). The change in HbA1c from baseline did not show statistical significance in the random-effects model, but showed statistical significance in favour of metformin in the fixed-effect model.

No significant difference was seen in change in fasting blood glucose (random MD 0.29 mmol/L, 95% CI -0.02 to 0.61;, n = 1301, 5 trials) or HbA1c (random MD -0.03%, 95% CI -0.17 to 0.10; n = 1444, 6 trials) with second-generation sulphonylureas compared to insulin.

Of retrospective subgroup analyses on pooled data from completed nateglinide randomized trials postbaseline safety evaluation was available from 2204 patients on monotherapy with nateglinide (n = 2,204), metformin (n = 436), and glyburide (n =293) . Glyburide 10 mg daily showed a significantly higher incidence of discontinuations and severe adverse events (SAEs) in patients over age 64 years with renal insufficiency (discontinuation, 10.5%; SAEs, 15.8%) compared with all glyburide patients (discontinuation, 3.8%; SAEs, 5.8%; both P < 0.05). Hypoglycaemic events in patients aged over 64 years were more common with glyburide (6.5%) than with nateglinide (2.2%) or metformin (0%).

A retrospective cohort study in the UK general practice research databaseincluded 91,521 people with diabetes. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001), and the risk was slightly higher with first than second generation sulphonylureas, and monotherapy with second generation sulphonylureas was associated with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001).

In a cohort study 33,243 sulfonylurea users chosen from 719 clinical practices in the United Kingdom were identified through the VAMP-Research database. A diagnosis of hypoglycemia during sulfonylurea therapy was recorded in 605 people over 34,052 person-years of sulfonylurea therapy, which converted into an annual risk of 1.8%. The risk was 1.4% in patients aged 20-64 years and 2.0% in patients aged over 65 years. The risk in glibenclamide users was higher than in users of other types of sulfonylureas uses. Duration of therapy, concomitant use of insulin, sulfonylurea-potentiating or antagonizing and concomitant use of beta-blockers were predictive of the risk of developing hypoglycemia.

Clinical comments

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Ədəbiyyat

1. Hemmingsen B, Schroll JB, Lund SS et al. WITHDRAWN: Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database Syst Rev 2015;(7):CD009008.
2. Del Prato S, Heine RJ, Keilson L et al. Treatment of patients over 64 years of age with type 2 diabetes: experience from nateglinide pooled database retrospective analysis. Diabetes Care 2003;26(7):2075-80.
3. Tzoulaki I, Molokhia M, Curcin V et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009;339():b4731.
4. van Staa T, Abenhaim L, Monette J. Rates of hypoglycemia in users of sulfonylureas. J Clin Epidemiol 1997;50(6):735-41.