Is Combination Sulfonylurea and Insulin Therapy Useful in NIDDM Patients?: A metaanalysis

Pugh, Jacqueline A.; Wagner, Mary L.; Sawyer, John B.; Ramı́rez, Gilbert; Tuley, Michael R.; Friedberg, Samuel J.

doi:10.2337/diacare.15.8.953

Cited by 96 publications

(55 citation statements)

References 28 publications

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“…34 In a meta-analysis of 17 clinical trials published from 1966 through 1991, a modest improvement in glycemic control and similar weight gain was demonstrated with sulfonylurea + insulin compared to insulin alone. 35 While these results were contrary to our finding that insulin alone led to lower HbA1c, the between-group differences were very small and likely not clinically different. This may in part be due to the smaller sample size of our groups overtime.…”

Section: Discussioncontrasting

confidence: 91%

“…36 Although there is evidence that combination therapy can decrease exogenous insulin requirements, this reduction is small. 35 In addition, there is little evidence that a modest reduction in insulin use is accompanied by significant differences in weight, hypoglycemia risk, or other long-term clinical benefits such as CVD or CKD prevention. Given our current findings of no large increased risk of clinical outcomes with the use of insulin alone compared with combination of sulfonylurea and insulin, the decision about which regimen to use should be tailored to the individual patient by addressing the potential benefit of using lower insulin dose in combined therapy versus the benefit of regimen simplicity and lower costs (one drug versus two).…”

Section: Discussionmentioning

confidence: 99%

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Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

et al. 2016

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BACKGROUND: Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited. OBJECTIVE: To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin. DESIGN: This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases. PARTICIPANTS: Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011. MAIN MEASURES:The association between insulin versus sulfonylurea + insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min. KEY FINDINGS: There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea + insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings. CONCLUSIONS: Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.

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Section: Discussioncontrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

et al. 2016

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“…In our study, only age was significantly different between responders and nonresponders to combined therapy. These results support the conclusions reached in review articles (25,27) that no clinical variable can predict the response to combined therapy in individual patients.…”

Section: Discussionsupporting

confidence: 90%

“…This fact may be attributed to the suppression of hepatic production of glucose by NPH insulin given at bedtime (11,24). A significant weight gain was observed during combined therapy as demonstrated by others (16,25), corresponding to an average of 2 kg. The increment in insulin doses in phase 3 did not cause an additional weight gain.…”

Section: Discussionmentioning

confidence: 74%

Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

Chazan

Gomes

2001

Braz J Med Biol Res

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To determine the effects of combined therapy of gliclazide and bedtime insulin on glycemic control and C-peptide secretion, we studied 25 patients with type 2 diabetes and sulfonylurea secondary failure, aged 56.8 ± 8.3 years, with a duration of diabetes of 10.6 ± 6.6 years, fasting plasma glucose of 277.3 ± 64.6 mg/dl and a body mass index of 27.4 ± 4.8 kg/m 2 . Patients were submitted to three therapeutic regimens lasting 2 months each: 320 mg gliclazide (phase 1), 320 mg gliclazide and bedtime NPH insulin (phase 2), and insulin (phase 3). At the end of each period, glycemic and C-peptide curves in response to a mixed meal were determined. During combined therapy, there was a decrease in all glycemic curve values (P<0.01). Twelve patients (48%) reached fasting plasma glucose <140 mg/dl with a significant weight gain of 64.8 kg (43.1-98.8) vs 66.7 kg (42.8-101.4) (P<0.05), with no increase in C-peptide secretion or decrease in HbA1. CPeptide glucose score (C-peptide/glucose x 100) increased from 0.9 (0.2-2.1) to 1.3 (0.2-4.7) during combined therapy (P<0.01). Despite a 50% increase in insulin doses in phase 3 (12 U (9-30) vs 18 U (11-60); P<0.01) only 3 patients who responded to combined therapy maintained fasting plasma glucose <140 mg/dl (P<0.02). A tendency to a higher absolute increase in C-peptide (0.99 (0.15-2.5) vs 0.6 (0-2.15); P = 0.08) and C-peptide incremental area (2.47 (0.22-6.2) vs 1.2 (0-3.35); P = 0.07) was observed among responders. We conclude that combined therapy resulted in a better glucose response to a mixed meal than insulin alone and should be tried in type 2 diabetic patients before starting insulin monotherapy, despite difficulties in predicting the response.

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“…There are several therapeutic schemes recommended for the treatment of type 2 diabetic patients. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Both non-insulinotropic and insulinotropic drugs are valid options for the crucial treatment of those patients with various pathophysiological origins of type 2 diabetes. 27 Because some degree of insulin deficiency is always present in an individual with diabetes type 2, we included metformin which is an agent known to influence insulin sensitivity without affecting insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

Comparative Assessment of the Treatment of Type 2 Diabetes Mellitus

et al. 2002

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Is Combination Sulfonylurea and Insulin Therapy Useful in NIDDM Patients?: A metaanalysis

Cited by 96 publications

References 28 publications

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes

Gliclazide and bedtime insulin are more efficient than insulin alone for type 2 diabetic patients with sulfonylurea secondary failure

Comparative Assessment of the Treatment of Type 2 Diabetes Mellitus

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