Therapeutic Comparison of Metformin and Sulfonylurea, Alone and in Various Combinations: A double-blind controlled study

Hermann, L. S.; Scherstén, Bengt; Bitzén, Per-Olof; Kjellström, Thomas; Lindgärde, Folke; Melander, Arne

doi:10.2337/diacare.17.10.1100

Cited by 314 publications

(209 citation statements)

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“…In contrast to other experimental studies [9,10,16], we observed no change in the course of weight after initiation of sulfonylurea treatment (Table 3). Weight loss is a common concomitant of the onset of metformin treatment [9,10,16], a finding which we cannot confirm either (Table 3). These results were possibly affected by the doctors' considerations about who would benefit from which drug treatment in our individualised treatment model.…”

Section: Weight Loss Due To Calorie Loss In Glucosuriacontrasting

confidence: 99%

“…It is commonly observed that treatment of type 2 diabetic patients with sulfonylureas [8][9][10] or insulin [10][11][12] is associated with weight gain. This effect of sulfonylureas and insulin could possibly aggravate the insulin-resistance syndrome associated with type 2 diabetes [2,13,14] and thereby counteract the otherwise beneficial effects of these agents.…”

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confidence: 99%

“…This effect of sulfonylureas and insulin could possibly aggravate the insulin-resistance syndrome associated with type 2 diabetes [2,13,14] and thereby counteract the otherwise beneficial effects of these agents. In contrast to insulin and sulfonylureas, treatment with metformin seems to be associated with weight reduction [8,15] or weight stabilisation [9,16].…”

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confidence: 99%

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Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus

et al. 2006

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Aims/hypothesis It is generally thought difficult for type 2 diabetic patients to lose weight. We monitored changes in patients' weight during the first 5 years after diabetes diagnosis in relation to initiation of antidiabetic treatment. Subjects and methods Data from 711 newly diagnosed diabetic patients aged 40 or over were analysed with a random-effect linear-regression model. Patients were included consecutively from a well-defined patient list in general practice. Results In 245 patients whose only treatment was advice on diet, an initial weight loss of 6 to 7 kg was largely maintained over 5 years. Patients receiving metformin (n=86) or sulfonylureas (n=330) maintained an average weight loss of 2 to 4 kg that was dependent on age and sex. Patients' weight did not change on initiation of treatment with sulfonylureas or metformin. Over 5 years, median HbA 1c increased from 7.0 to 7.8% (reference range 5.4-7.4%) in the diet-alone group. HbA 1c was approximately 1 percentage point higher for most of the other treatment groups. Conclusions/interpretation In newly diagnosed type 2 diabetic patients, long-term weight loss was common and weight loss was not affected by sulfonylurea treatment. The measurements in the study are taken from treatment results achieved in the general population of diabetic patients, who are rarely treated in secondary care and seldom the subject of research; the results thus indicate that weight reduction is a practicable treatment in diabetic patients.

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Section: Weight Loss Due To Calorie Loss In Glucosuriacontrasting

confidence: 99%

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Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus

et al. 2006

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“…It also has beneficial effects in cardiovascular disease, impaired glucose tolerance and polycystic ovary syndrome through an insulinsensitizing effect [1] . However, metformin therapy is characterized by considerable inter-individual variability in clinical efficacy [2] . Some studies have shown that metformin is not metabolized but is transported by at least two organic cation transporters (OCTs), OCT1 and OCT2 [3,4] .…”

Section: Introductionmentioning

confidence: 99%

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin

Liu

Zheng

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM). Methods: The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformintreated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzymeelectrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured. Results: The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29±0.45 mmol/L vs 1.18±0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18±0.15 vs 1.04±0.27 mmol/L, P=0.008) and GG genotypes (1.40±0.51 vs 1.19±0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group. Conclusion: There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.

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“…In type 2 diabetic patients with baseline HbA 1c (A1C) 8.5-9.0%, monotherapy with metformin (4,5) or sulfonylureas (6,7) reduces the A1C by ϳ1.5-2%. Addition of metformin to a sulfonylurea or vice versa provides a completely additive effect and decreases the A1C to Ͻ7.0% in ϳ60 -70% of patients (4,8,9). Mechanistically, optimal treatment in the remaining 30 -40% of individuals who do not achieve adequate glycemic control on metformin/sulfonylurea therapy remains unclear (8,10).…”

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Comparison of Glargine Insulin Versus Rosiglitazone Addition in Poorly Controlled Type 2 Diabetic Patients on Metformin Plus Sulfonylurea

et al. 2006

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OBJECTIVE -We sought to examine the mechanisms by which the addition of glargine insulin or rosiglitazone improves glycemic control in type 2 diabetic subjects poorly controlled on maximally effective doses of metformin plus sulfonylurea. RESULTS -A1C and FPG decreased similarly in the glargine insulin (9.1 Ϯ 0.4 to 7.6 Ϯ 0.3% and 212 Ϯ 14 to 139 Ϯ 5 mg/dl, respectively, both P Ͻ 0.0001) and rosiglitazone (9.4 Ϯ 0.3 to 7.6 Ϯ 0.4% and 223 Ϯ 14 to 160 Ϯ 19 mg/dl, respectively, both P Ͻ 0.005) groups. After 4 months, endogenous glucose production (EGP) declined similarly with glargine insulin (2.27 Ϯ 0.10 to 1.73 Ϯ 0.12 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.0001) and rosiglitazone (2.21 Ϯ 0.12 to 1.88 Ϯ 0.12 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P ϭ 0.01). The hepatic insulin resistance index declined in the rosiglitazone group (32 Ϯ 3 to 21 Ϯ 1 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ϫ U/ml, P ϭ 0.03 vs. baseline and P Ͻ 0.05 vs. glargine insulin) and did not change in the glargine group (22 Ϯ 5 to 20 Ϯ 3 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ϫ U/ml, P ϭ NS). At 4 months, glargine insulin (3.6 Ϯ 0.5 to 4.2 Ϯ 0.4 mg ⅐ kg RESEARCH DESIGN AND METHODS Ϫ1⅐ min Ϫ1 , P Ͻ 0.01) and rosiglitazone (2.7 Ϯ 0.3 to 3.8 Ϯ 0.3 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 , P Ͻ 0.0005) increased R d , but the increment was greater in the rosiglitazone group (P Ͻ 0.05). Diastolic blood pressure was reduced only by rosiglitazone (P Ͻ 0.01).CONCLUSIONS -Triple therapy with glargine insulin or rosiglitazone similarly reduced A1C, primarily by suppressing basal EGP (hepatic). Glargine insulin reduced basal EGP by increasing plasma insulin levels, while rosiglitazone decreased basal hepatic glucose production by improving hepatic insulin sensitivity.

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Therapeutic Comparison of Metformin and Sulfonylurea, Alone and in Various Combinations: A double-blind controlled study

Cited by 314 publications

References 18 publications

Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus

Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin

Comparison of Glargine Insulin Versus Rosiglitazone Addition in Poorly Controlled Type 2 Diabetic Patients on Metformin Plus Sulfonylurea

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