Sulphonylurea Failure in Type 2 Diabetes: Treatment with a Basal Insulin Supplement

Holman, Rury R.; Steemson, J; Turner, R. C.

doi:10.1111/j.1464-5491.1987.tb00909.x

Cited by 72 publications

(26 citation statements)

References 22 publications

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“…The progressive nature of the hyperglycemia seen in type 2 diabetes (3) is exemplified by the evidence herein that 53% of patients with newly diagnosed diabetes treated with sulfonylurea therapy require additional treatment within 6 years to maintain FPG levels Ͻ6.0 mmol/l. A basal insulin regimen was used in this study because it is highly effective in suppressing basal hepatic glucose production (13,14). The overall improvement seen in glycemic control may reflect increased glucose-mediated release potentiated by the sulfonylureas in the setting of adequate basal insulin implementation.…”

Section: Hypoglycemiamentioning

confidence: 99%

Sulfonylurea Inadequacy

et al. 2002

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FOR THE U.K. PROSPECTIVE DIABETES STUDY GROUPOBJECTIVE -To evaluate the efficacy of the addition of insulin when maximal sulfonylurea therapy is inadequate in individuals with type 2 diabetes.RESEARCH DESIGN AND METHODS -Glycemic control, hypoglycemia, and body weight were monitored over 6 years in 826 patients with newly diagnosed type 2 diabetes in 8 of 23 U.K. Prospective Diabetes Study (UKPDS) centers that used a modified protocol. Patients were randomly allocated to a conventional glucose control policy, primarily with diet (n ϭ 242) or an intensive policy with insulin alone (n ϭ 245), as in the main study. However, for patients randomized to an intensive policy with sulfonylurea (n ϭ 339), insulin was added automatically if the fasting plasma glucose remained Ͼ108 mg/dl (6.0 mmol/l) despite maximal sulfonylurea doses.RESULTS -Over 6 years, ϳ53% of patients allocated to treatment with sulfonylurea required additional insulin therapy. Median HbA 1c in the sulfonylurea Ϯ insulin group was significantly lower (6.6%, interquartile range [IQR] 6.0 -7.6) than in the group taking insulin alone (7.1%, IQR 6.2-8.0; P ϭ 0.0066), and significantly more patients in the sulfonylurea Ϯ insulin group had an HbA 1c Ͻ7% (47 vs. 35%, respectively; P ϭ 0.011). Weight gain was similar in the intensive therapy groups, but major hypoglycemia occurred less frequently over all in the sulfonylurea (Ϯ insulin) group compared with the insulin alone group (1.6 vs. 3.2% per annum, respectively; P ϭ 0.017).CONCLUSIONS -Early addition of insulin when maximal sulfonylurea therapy is inadequate can significantly improve glycemic control without promoting increased hypoglycemia or weight gain. Diabetes Care 25:330 -336, 2002T he U.K. Prospective Diabetes Study (UKPDS) showed that intensive control of blood glucose with sulfonylurea or insulin, and with metformin in overweight patients, substantially reduced the risk of diabetic complications (1). The intensive glucose control policy used in the first 15 UKPDS centers (Glucose Study 1) required patients to remain on their allocated monotherapy, unless fasting plasma glucose (FPG) levels increased to Ͼ15 mmol/l or hyperglycemic symptoms ensued, to evaluate specific advantages or disadvantages of individual therapies. With the realization that progressive hyperglycemia was occurring in all randomized groups (2-4) and that additional therapy might be desirable at the stage of sulfonylurea inadequacy (5) rather than sulfonylurea failure, a modified protocol (Glucose Study 2) was introduced in the last eight UKPDS centers (6). This protocol, the aim of which was to determine whether a more aggressive glucose control policy could minimize hyperglycemic progression, differed only in that insulin therapy was added immediately in patients allocated to sulfonylurea therapy if maximal doses did not maintain FPG levels Ͻ108 mg/dl (6.0 mmol/l).A meta-analysis of randomized controlled trials (7) has shown that combining sulfonylurea and insulin therapy can improve metabolic control with significantly smal...

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Section: Hypoglycemiamentioning

confidence: 99%

Sulfonylurea Inadequacy

et al. 2002

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“…Certain proposed deleterious effects of insulin support the argument that liberal use of insulin should be avoided (Holman et al 1987;Karam 1992;Quatraro et al 1986;Turner et al 1986). Such deleterious effects of insulin include bodyweight gain from increased lipogenesis, increased atherosclerosis (growth factor-like properties, effects on endothelial cell uptake and synthesis of cholesterol, and smooth muscle proliferation) and potentiation of hypertension.…”

Section: Insulinmentioning

confidence: 87%

Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications

Ilarde¹,

Tuck

1994

Drugs & Aging

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Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually. The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies. Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight. Sulphonylurea drugs stimulate insulin secretion from beta-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. alpha-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate. Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.

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“…It has been previously reported that the addition of metformin is less effective than the addition of ultralente insulin in NIDDM patients with secondary failure to sulfonylureas (11). Differences in the type of long-acting insulin used (NPH vs. ultralente) and in its dosage (11.7 ± 1.0 U/day in our study vs. 32.5 ± 6.6 U/day in the study of Holman et al [11]) and differences in the sulfonylurea used may explain the contrasting results in the two studies.…”

Section: Phasementioning

confidence: 99%