Sulfonylurea Combination Therapy Research Articles

Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes.

Multidrug and toxin extrusion transporter 1 (MATE1), encoded by the SLC47A1 gene and single nucleotide polymorphisms of organic cation transport 1, may impact metformin's responsiveness and side effects. Inward-rectifier potassium channel 6.2 (Kir 6.2) subunits encoded by KCNJ11 may affect the response to sulfonylurea. This study aimed to evaluate the association between SLC22A1 rs72552763 and rs628031, SLC47A1 rs2289669 and KCNJ11 rs5219 genetic variations with sulfonylurea and metformin combination therapy efficacy and safety in Egyptian type 2 diabetes mellitus patients. This study was conducted on 100 cases taking at least one year of sulfonylurea and metformin combination therapy. Patients were genotyped via the polymerase chain reaction-restriction fragment length polymorphism technique. Then, according to their glycated hemoglobin level, cases were subdivided into non-responders or responders. Depending on metformin-induced gastrointestinal tract side effects incidence, patients are classified as tolerant or intolerant. KCNJ11 rs5219 heterozygous and homozygous mutant genotypes, SLC47A1 rs2289669 heterozygous and homozygous mutant genotypes (AA and AG), and mutant alleles of both polymorphisms were significantly related with increased response to combined therapy. Individuals with the SLC22A1 (rs72552763) GAT/del genotype and the SLC22A1 (rs628031) AG and AA genotypes were at a higher risk for metformin-induced gastrointestinal tract adverse effects. The results implied a role for SLC47A1 rs2289669 and KCNJ11 rs5219 in the responsiveness to combined therapy. SLC22A1 (rs628031) and (rs72552763) polymorphisms may be associated with increased metformin adverse effects in type 2 diabetes mellitus patients.

EVALUASI ORAL ANTIDIABETIK PADA PASIEN DIABETES MELITUS TIPE 2 DI RSUD "X" LAMONGAN

Diabetes Mellitus Type 2 is a metabolic disorder characterized by an increase in blood sugar due to decreased insulin secretion by pancreatic beta cells and or insulin function disorders (insulin resistance). This study aims to evaluate oral antidiabetics in patients with type 2 diabetes mellitus at the Regional General Hospital dr. Soegiri Lamongan. This research design is descriptive with a population of all type 2 diabetes mellitus patients from July to August 2019 using a total sampling technique. The number of samples in this study were 64 patients. The results showed that the most prescribed oral antidiabetic in type 2 diabetes mellitus patients at the RSUD in Lamongan was an oral combination of antidiabetic, namely Gliclazid and Metformin (29.70%), in terms of the correct dose and method of administration of the drug, in accordance with the guidelines in the Ministry of Health. and FRS (100%), in the data of patients who experienced a decrease in GDA, it was seen that the combination therapy of sulfonylurea and biguanide compared to single therapy was 92.5%. Keywords: Diabetes Mellitus Type 2, Oral Antidiabetic, Blood Glucose

Association Between Metformin and Sulfonylurea Monotherapies and Cancer Incidence: A Real-World Cohort Study in Shanghai, China.

IntroductionPrevious studies have shown that patients with type 2 diabetes mellitus have an increased risk of cancer. The use of antidiabetic medication (ADM) may play an important role in the cancer development. The relationship between oral ADM and cancer incidence has not been investigated in type 2 diabetes mellitus patients in mainland China yet.MethodsA community-based diabetes cohort was extracted from the Shanghai Community Diabetes Management System database, which is a patient registry from general practices. The cohort included 2353 newly onset type 2 diabetes mellitus patients from 2006 to 2010 aged 35 years or more. Patients were grouped into nonusers of antidiabetic medication (n = 722), metformin monotherapy (n = 374), sulfonylurea monotherapy (n = 653), metformin and sulfonylurea combination therapy (n = 302), and other medication therapies (n = 302) on the basis of initial treatment type at registry entry. Cancer incidence was identified from the Shanghai Cancer Registry Organization. Comparisons between monotherapy and nonuser of medication were conducted using Cox proportional hazards models.ResultsA total of 94 cancer cases were identified during 5 years median follow-up. Compared with nonusers, sulfonylurea monotherapy was associated with significantly lower risk of cancer [adjusted HR = 0.50 (95% CI 0.29–0.85)] whereas risk was 49% lower with metformin monotherapy [adjusted HR = 0.51 (95% CI 0.27–0.99)].ConclusionThe real-world evidence suggested that the use of metformin or sulfonylurea was associated with lower risk of cancer incidence in a cohort of newly onset type 2 diabetes mellitus patients.

Comparison of Antidiabetic Regimens in Patients with Type 2 Diabetes Uncontrolled by Combination Therapy of Sulfonylurea and Metformin: Results of the MOHAS Disease Registry in Korea.

BackgroundThe aim of this study was to investigate the glucose-lowering efficacy of antidiabetic treatments in patients with type 2 diabetes mellitus (T2DM) uncontrolled by sulfonylurea plus metformin.MethodsThis open-label, multicenter, prospective, observational study was conducted in 144 centers in Korea, from June 2008 to July 2010, and included patients with T2DM who had received sulfonylurea and metformin for at least 3 months and had levels of glycosylated hemoglobin (HbA1c) >7.0% in the last month. Data of clinical and biochemical characteristics were collected at baseline and 6 months after treatment. The treatment option was decided at the physician's discretion. Subjects were classified into the following three groups: intensifying oral hypoglycemic agents (group A), adding basal insulin (group B), or starting intensified insulin therapy (group C).ResultsOf 2,995 patients enrolled, 2,901 patients were evaluated, and 504 (17.4%), 2,316 (79.8%), and 81 patients (2.8%) were classified into groups A, B, and C, respectively. Subjects in group C showed relatively higher baseline levels of HbA1c and longer duration of diabetes. The mean decrease in HbA1c level was higher in the insulin treated groups (−0.9%±1.3%, −1.6%±1.3%, and −2.4%±2.3% in groups A, B, and C, respectively, P=0.042). The proportion of patients who achieved target HbA1c <7.0% was comparable among the groups; however, intensified insulin therapy seemed to be the most effective in achieving the target HbA1c of 6.5%.ConclusionThese findings suggest that insulin-based therapy will be an important option in the improved management of Korean patients with T2DM whose glycemic control is not sufficient with sulfonylurea and metformin.

DPP-4 Inhibitors and Heart Failure: Some Reassurance, Some Uncertainty.

The American Diabetes Association’s Standards of Medical Care in Diabetes—2016 recommends the use of dipeptidyl peptidase 4 (DPP-4) inhibitors in combination with metformin as a second- or third-line treatment for type 2 diabetes (1). Owing to their relatively high costs, many jurisdictions restrict their use to patients whose glycemia remains poorly controlled on metformin–sulfonylurea combination therapy. By inhibiting DPP-4 activity, these agents increase postprandial incretin concentrations, thereby increasing insulin secretion and decreasing glucagon secretion (1). With intermediate efficacy, a low risk of hypoglycemia, neutral effects on body weight, and relatively rare adverse effects (1), their use has increased considerably since their 2006 entry into the U.S. market (2). Nevertheless, concerns remain regarding their potential association with serious adverse effects including acute pancreatitis (3), pancreatic cancer (3), and heart failure (HF) (4). The potential increased risk of HF with DPP-4 inhibitors was reported in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, which randomized 16,492 patients with type 2 diabetes and either a history of cardiovascular disease (CVD) or multiple CVD risk factors to saxagliptin (Onglyza) or placebo (5) (Table 1). Patients randomly assigned to saxagliptin unexpectedly had a significantly higher risk of hospitalization for HF (hazard ratio [HR] 1.27 [95% CI 1.07–1.51]), a prespecified component of the secondary composite end point. This increased risk was clustered in the first year of follow-up (HR 1.46 [95% CI 1.15–1.88]) with no increase thereafter (6). View this table: Table 1 Data from randomized placebo-controlled trials of DPP-4 inhibitors and the risk of HF The increased HF risk in SAVOR-TIMI 53 was not observed in subsequent trials (Table 1). In the Examination …

Factors Predictive of Weight Gain and Implications for Modeling in Type 2 Diabetes Patients Initiating Metformin and Sulfonylurea Combination Therapy.

Introduction The objectives of this study were to (a) assess the factors associated with weight gain in a population of type 2 diabetes patients escalating from metformin (M) to M+ sulfonylurea (M + S) and (b) evaluate whether healthcare resource utilization associated with being overweight or obese is underestimated in typical health economic evaluations.Methods The study was a retrospective cohort study using UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (CPRD/HES) data. The association between baseline phenotypic factors and weight gain was assessed using logistic regression. Hospitalization incidence rates per 1000 person-years for major diabetes-related complications according to body mass index (BMI) at baseline were estimated from the data (observed) and compared to those obtained from a validated diabetes model (predicted).Results11,071 patients were included in the analysis; approximately 40% gained weight in the first year following escalation to M + S. Baseline age, HbA1c and gender were found to be predictors of weight gain [odds ratios 0.99 (1-year increment), 1.11 (1% increment) and 0.81 (female vs male), respectively, p < 0.001]. Observed vs predicted incidence rates of hospitalization were 265 vs 13 (normal), 297 vs 31 (overweight), 223 vs 50 (obese) and 378 vs 41 (severe obese).ConclusionThis analysis suggests there are identifiable patient characteristics predictive of weight gain that may be informative to clinical and economic decision making in the context of patients escalating from M to an M + S regimen. Hospital admissions in people with type 2 diabetes were generally under-predicted. A particular focus of future research should be the need for diabetes models to make the likelihood of experiencing an event conditional on BMI.FundingTakeda Development Centre Europe Ltd., UK.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-015-0134-y) contains supplementary material, which is available to authorized users.

Retrospective analysis of safety and efficacy of liraglutide monotherapy and sulfonylurea-combination therapy in Japanese type 2 diabetes: Association of remaining β-cell function and achievement of HbA1c target one year after initiation

AimsThe GLP-1 receptor agonist liraglutide improves impaired pancreatic β-cell function, thereby exerting glucose-lowering effects. However, the association of remaining β-cell function with long-term therapeutic efficacy of liraglutide remains largely unknown. MethodsPatients with type 2 diabetes who started liraglutide as monotherapy or sulfonylurea-combination therapy were retrospectively analyzed to identify possible associations of indices related to β-cell function including increments of C-peptide immunoreactivity in glucagon stimulation test (GST-ΔCPR) with achievement of HbA1c <7.0% at 54weeks after liraglutide initiation. ResultsAmong 165 subjects continuing liraglutide for 54weeks, 66 received additional oral anti-diabetic drugs (OADs) during the period. Of those continuing liraglutide without receiving additional OADs, 41 subjects achieved HbA1c <7.0% at 54weeks, while 49 subjects did not. Subjects achieving HbA1c <7.0% showed higher values of GST-ΔCPR. Receiver-operating analysis revealed 2.34ng/mL as the cut-off value for HbA1c <7.0% achievement in these subjects. Subjects with GST-ΔCPR >2.34ng/mL showed continuous and substantial HbA1c reduction throughout the 54weeks. In Kaplan–Meier analysis, subjects with GST-ΔCPR >2.34ng/mL showed longer therapeutic durability of initial liraglutide therapy with no additional OADs or insulin. ConclusionsDespite numerous limitations, these results indicate that long-term efficacy of liraglutide is associated with remaining β-cell function at initiation.

Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies

Objective: To assess the safety and efficacy of long-term administration of teneligliptin alone and in combination with oral antidiabetic drugs in Japanese type 2 diabetes mellitus (T2DM) patients with insufficient glycemic control.Methods: This post-hoc pooled analysis used data from two Phase III clinical studies involving 702 Japanese patients. We evaluated teneligliptin as monotherapy and combined with a sulfonylurea, glinide, biguanide, or α-glucosidase inhibitor. Safety measures included adverse events (AEs), adverse reactions and hypoglycemia. The main efficacy measure was the change in glycated hemoglobin (HbA1c) from baseline.Results: Incidences of AEs and adverse reactions were similar among the teneligliptin monotherapy group and all combination therapy groups except the combination with sulfonylurea. Hypoglycemia was more frequent in the sulfonylurea combination therapy group than in other groups. Teneligliptin administered once daily as monotherapy or combination therapy resulted in a decrease in HbA1c, which was maintained for 52 weeks. Bodyweight showed no change or a slight increase at the end of 52 weeks in all groups.Conclusions: This pooled analysis provides evidence for the safety and efficacy of long-term use of teneligliptin as monotherapy or combination therapy in Japanese T2DM patients.

Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 Diabetes

Context:The safety of insulin in the treatment of type 2 diabetes mellitus (T2DM) has recently undergone scrutiny.Objective:The objective of the study was to characterize the risk of adverse events associated with glucose-lowering therapies in people with T2DM.Design and Setting:This was a retrospective cohort study using data from the UK General Practice Research Database, 2000–2010.Patients:Patients comprised 84 622 primary care patients with T2DM treated with one of five glucose-lowering regimens: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. There were 105 123 exposure periods.Main Outcome Measures:The risk of the first major adverse cardiac event, first cancer, or mortality was measured. Secondary outcomes included these individual constituents and microvascular complications.Results:In the same model, and using metformin monotherapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for sulfonylurea monotherapy (1.436, 95% confidence interval [CI] 1.354–1.523), insulin monotherapy (1.808, 95% CI 1.630–2.005), and insulin plus metformin (1.309, 95% CI 1.150–1.491). In glycosylated hemoglobin/morbidity subgroups, patients treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.469 (95% CI 0.978–2.206) to 2.644 (95% CI 1.896–3.687). For all secondary outcomes, insulin monotherapy had increased aHRs: myocardial infarction (1.954, 95% CI 1.479–2.583), major adverse cardiac events (1.736, 95% CI 1.441–2.092), stroke (1.432, 95% CI 1.159–1.771), renal complications (3.504, 95% CI 2.718–4.518), neuropathy (2.146, 95% CI 1.832–2.514), eye complications (1.171, 95% CI 1.057–1.298), cancer (1.437, 95% CI 1.234–1.674), or all-cause mortality (2.197, 95% CI 1.983–2.434). When compared directly, aHRs were higher for insulin monotherapy vs all other regimens for the primary end point and all-cause mortality.Conclusions:In people with T2DM, exogenous insulin therapy was associated with an increased risk of diabetes-related complications, cancer, and all-cause mortality. Differences in baseline characteristics between treatment groups should be considered when interpreting these results.

Comparative evaluation of effects of combined oral anti-diabetic drugs (sulfonylurea plus pioglitazone and sulfonylurea plus metformin) over lipid parameters in type 2 diabetic patients

Background: Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Dyslipidemia, which affects almost 50% of patients with type 2 diabetes, is a cardiovascular risk factor characterized by elevated triglyceride levels, low high-density lipoprotein (HDL) cholesterol levels, and a preponderance of small, dense, low-density lipoprotein (LDL) particles. In addition to their glucose-lowering properties, oral anti-diabetic agents may have effects on lipid levels, especially triglycerides (TGs), HDL-C, LDL-C and total cholesterol levels. Methods: A prospective, open-labeled, randomized, parallel-group study was carried out in sizable number of patients (n=40) of established type 2 diabetes on combined oral anti-diabetic drugs, to investigate the effects of combined oral anti-diabetic on lipid parameters who was not receiving any hypolipidemic agent in addition. Results: Statistically significant mean reduction of triglycerides (TGs) of 25.1mg/dl (a 15.30% reduction from baseline value) and by 13.5 mg/dl (a 8.94% reduction from baseline value) in the SU (sulfonylurea) plus PIO (pioglitazone) and SU plus MET (metformin) group respectively. Present study also shows improvement in HDL cholesterol with SU plus PIO group by 13.18% which is almost twice that observed in SU plus MET group (8.06%). Present study also shows increase in LDL cholesterol with SU plus PIO group by 2.10%, is just opposite to SU plus MET group (4.92 % decrease). With SU plus PIO group, a statistically significant mean reduction of total cholesterol (TC) of 8.33mg/dl (5.14 % decrease) and by 7.62 mg/dl (4.28% decrease) in the SU plus MET group. Conclusions: Pioglitazone, a thiazolidinedione, has been shown to improve the lipid profile in patients with type 2 diabetes by increasing HDL-C levels and by decreasing triglyceride and total cholesterol levels in monotherapy or combination regimens with sulfonylurea. Metformin also has been shown to reduce LDL-C, TC, and TG levels and increase HDL-C levels in monotherapy and in combination regimens with sulfonylurea. In contrast, LDL cholesterol levels mild increase with pioglitazone monotherapy or with SU combination therapy. Thus the results of this study have demonstrated that SU plus pioglitazone is an effective combination regimen for patients insufficiently treated with SU monotherapy and may provide possible positive effects on other coronary risk factors/ dyslipidemias associated with the type 2 diabetes.

Liraglutide in adults with type 2 diabetes: global perspective on safety, efficacy and patient preference.

Incretin-based therapies have been gaining much attention recently as a new class of therapeutics for type 2 diabetes worldwide. Among them, glucagon-like peptide-1 receptor agonist liraglutide has been rapidly increasing its global usage. Once daily injection of liraglutide significantly ameliorates glycemic control in patients with type 2 diabetes by enhancing insulin secretion and suppressing glucagon secretion glucose-dependently. Liraglutide delays gastric emptying and suppresses food intakes, both of which contribute to glucose lowering and weight reduction. Efficacy and safety of liraglutide in management of type 2 diabetes have been well documented in several key clinical trials such as series of phase 3 Liraglutide Effect and Action in Diabetes (LEAD) trials, and the liraglutide-versus-sitagliptin trial. Recent two trials dealing with monotherapy and sulfonylurea combination therapy on Japanese patients with type 2 diabetes furthermore indicate liraglutide’s effectiveness in non-obese diabetes. In this review, we summarize results from such clinical trials, and discuss efficacy and safety of liraglutide in management of type 2 diabetes in various countries, along with a pitfall of liraglutide usage in real clinical setting.

The effect of combination therapy of sulfonylurea, metformin, and acarbose in type 2 diabetes mellitus patients

Diabetes mellitus is a complex disorder that involves multiple pathophysiological defects. As the disease progresses, further functional decline in β-cell is apparent. In most cases, patients on oral antidiabetic therapy will require not only an increase in dose, but also the addition of a second or third oral agent. The aim of this study was to evaluate the effectiveness and safety of triple therapy with sulfonylurea, metformin, and acarbose in patients with poorly controlled glycemia. The study design was a prospective observational study in 49 type 2 diabetic patients followed in Department of Endocrinology RSUP Dr Sardjito Indonesia from May 2007 to September 2008. Patients with hypertension were included if their blood pressure was well controlled with antihypertensive medication. All patients with documented gastrointestinal disease were excluded. At baseline and at 3-month intervals, levels of HbA1C, fasting and postprandial plasma glucose, hypoglycemic episodes, and edverse event were evaluated. Fourty nine patients, 22 men and 27 women, aged 62.84 + 7.85 years, diabetes duration of 11.92 + 6.09 years were studied. The initial HbA1C level was 8.08 + 1.89 % which significantly increased to 8.73 + 2.37 % (p<0.05). Only 32.98 % of subjects achieved target value of HbA1C (≤ 7 %). Fasting and post-prandrial plasma glucose values were increased from 160.39 + 60.25 mg/dL to 170.71 + 56.60 mg/dL and 210.31 + 75.88 mg/dL to 218.67 + 75.03 mg/dL respectively, but not significantly different. Acarbose was more frequently associated with flatulence (46 %) and abdominal bloating (12 %), metformin with flatulence (12 %), nausea (14 %), diarrhea (2 %) and abdominal discomfort (6 %). In conclusion, combination therapy of sulfonylurea, metformin, and acarbose in type 2 diabetic patients with poorly controlled glycemia can cause the additive risk of adverse events. Key words : triple therapy, glycemic control, type 2 diabetes mellitus

Is the Combination of Sulfonylureas and Metformin Associated With an Increased Risk of Cardiovascular Disease or All-Cause Mortality?

OBJECTIVE—Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes.RESEARCH DESIGN AND METHODS—A MEDLINE search (January 1966–July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of CVD or all-cause mortality. From 299 relevant reports, 9 were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of CVD and/or mortality was reported, and adjusted relative risk (RR) or equivalent (hazard ratio and odds ratio) and corresponding variance or equivalent was reported.RESULTS—The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88–1.62) for all-cause mortality, 1.29 (0.73–2.27) for CVD mortality, and 1.43 (1.10–1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events).CONCLUSIONS—The combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy, or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone.

Effect of Acarbose, an Alpha-Glucosidase Inhibitor, on Serum Lipoprotein Lipase Mass Levels and Common Carotid Artery Intima-Media Thickness in Type 2 Diabetes Mellitus Treated by Sulfonylurea

Previous reports indicate that serum lipoprotein lipase mass levels (LPL mass) and common carotid artery intima-media thickness (CCA-IMT) are independent predictors of atherosclerotic diseases. The aim of this study was to examine the effects of combination therapy of sulfonylurea and acarbose on LPL mass and CCA-IMT. Eighty-four patients with type 2 diabetes mellitus, who were treated with only sulfonylureas and showed CCA-IMT of more than 0.9 mm at baseline, were selected and randomly divided into two groups. One group was administered acarbose 300 mg/day for 12 months (acarbose group, n=41), and the other group was not administered acarbose (non-acarbose group, n=43). After 12 months, a significant increase in LPL mass and a significant decrease in CCA-IMT were observed in the acarbose group (1.024 to 0.964 mm), but no significant changes were observed in the non-acarbose group. In a subgroup analysis of patients with HbA1c improved by 0.5% or more, the increase of LPL mass and decrease of CCA-IMT was significantly greater in the acarbose group than in the non-acarbose group although the changes in HbA1c were similar in two groups. We concluded that reducing postprandial hyperglycemia might increase LPL mass levels and might be useful to prevent macroangiopathy in type 2 diabetic patients treated by sulfonylurea.

Cost-effectiveness of Rosiglitazone Combination Therapy for the Treatment of Type 2 Diabetes Mellitus in the UK

Recent clinical trial results have demonstrated that, in patients with type 2 diabetes, second-line treatment of rosiglitazone in combination with metformin can lead to significant improvements in the control of fasting plasma glucose/ glycosylated haemoglobin A1c (HbA1c) after the failure of metformin monotherapy. Our objective was to assess the cost-effectiveness of the use of rosiglitazone in combination with metformin in overweight and obese patients with type 2 diabetes in the UK, failing to maintain glycaemic control with metformin monotherapy compared with conventional care using metformin in combination with sulfonylurea. The Diabetes Decision Analysis of Cost--type 2 (DiDACT) model, an established long-term economic model of type 2 diabetes, which projects the relationship between treatment and HbA1c over extended periods, was used to determine the health outcomes and economic impact for matched age and sex cohorts of 1000 patients with type 2 diabetes. The perspective was that of the UK National Health Service and all costs were in UK pounds sterling. Treatment with rosiglitazone in combination with metformin provides better glycaemic control over the remaining lifetime of patients than metformin and sulfonylurea combination therapy. Patients treated with rosiglitazone combination therapy were predicted to have a longer life expectancy, gaining 123 and 140 additional life years per 1000 patients in the obese and overweight cohorts, respectively. Improvements in morbidity and a delay in the start of insulin therapy resulted in a projected improvement in quality of life. These effects combine with projected improved survival to yield 131 and 209 additional quality-adjusted life-years (QALYs) per 1000 patients in the obese and overweight cohorts, respectively. Discounted incremental cost-effectiveness ratios were estimated at pounds 16,700 per QALY gained for the obese cohort and pounds 11,600 per QALY gained for the overweight cohort. The model predicts that rosiglitazone in combination with metformin is a cost-effective treatment in the UK for both obese and overweight patients failing on metformin monotherapy, compared with conventional therapy using metformin in combination with sulfonylurea.

Suppertime 70/30 insulin and sulfonylurea combination therapy for Japanese type 2 diabetic patients

Suppertime 70/30 insulin and sulfonylurea combination therapy for Japanese type 2 diabetic patients

Efficacy of Insulin and Sulfonylurea Combination Therapy in Type II Diabetes

Numerous studies demonstrate the efficacy of the combination therapy of insulin and sulfonylurea in subjects with type II diabetes mellitus. However, two recent meta-analyses of randomized trials during the last decade provided inconsistent conclusions and failed to resolve the controversy. To assess the efficacy of insulin and sulfonylurea combination therapy in type II diabetes mellitus by performing meta-analysis of only the controlled studies selected according to specific strict criteria. A computerized literature survey was conducted using the MEDLINE database from January 1980 through March 1992 with the search headings of "sulfonylurea" and "insulin" and "combination therapy in diabetes mellitus. "A manual search was also performed using references from each retrieved report. Case reports, review articles, editorials, and citations reported in non-English-language journals without English translations were excluded. Forty-three citations were obtained. Four strict inclusion criteria were used to select studies: randomized, placebo-controlled trials (oral agent plus insulin vs placebo plus insulin); homogeneous target population (subjects with type II diabetes); intervention using the same sulfonylurea agent in a combination therapy; and uniform outcome measures to evaluate efficacy such as body weight; values for serum glucose, glycohemoglobin, and C peptide; daily insulin dosage; and lipid concentrations. More stringent qualitative subcriteria were then used to eliminate bias in the final unanimous selection by two blinded reviewers. Data were pooled and analyzed using Student's t test and Winer's combined test. Sixteen studies satisfied the inclusion criteria. Metabolic control improved with the combination therapy as reflected by a significant lowering of fasting serum glucose values (P < .01) and glycohemoglobin concentrations (P < .025). Moreover, improved metabolic control was achieved with a significantly smaller daily insulin dose (P < .01) and without a significant change in body weight. Finally, the combination therapy enhanced the endogenous insulin secretion as expressed by an increase in fasting serum C peptide concentration (P < .05). Combination therapy with insulin and sulfonylurea may be a more appropriate and a suitable option to insulin monotherapy in subjects with non-insulin-dependent diabetes in whom primary or secondary failure to sulfonylurea developed. It may also be a more cost-effective way of long-term management in this group of subjects, especially in the elderly.

Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials

Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials