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Quantifying the effect of metformin treatment and dose on glycemic control.

ABSTRACT: Metformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA(1c)) levels in all types of diabetes and examine the impact of differing doses on glycemic control.MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks' duration in which diabetic patients were treated with either metformin monotherapy or as an add-on therapy. Data on change in HbA(1c) were pooled in a meta-analysis. Data from dose-comparison trials were separately pooled.A total of 35 trials were identified for the main analysis and 7 for the dose-comparison analysis. Metformin monotherapy lowered HbA(1c) by 1.12% (95% CI 0.92-1.32; I(2) = 80%) versus placebo, metformin added to oral therapy lowered HbA(1c) by 0.95% (0.77-1.13; I(2) = 77%) versus placebo added to oral therapy, and metformin added to insulin therapy lowered HbA(1c) by 0.60% (0.30-0.91; I(2) = 79.8%) versus insulin only. There was a significantly greater reduction in HbA(1c) using higher doses of metformin compared with lower doses of metformin with no significant increase in side effects.Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA(1c) used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.

SUBMITTER: Hirst JA

PROVIDER: S-EPMC3263873 | biostudies-other | 2012 Feb

REPOSITORIES: biostudies-other

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Quantifying the effect of metformin treatment and dose on glycemic control.

Hirst Jennifer A JA Farmer Andrew J AJ Ali Raghib R Roberts Nia W NW Stevens Richard J RJ

Diabetes care 20120201 2

<h4>Objective</h4>Metformin is the first-line oral medication recommended for glycemic control in patients with type 2 diabetes. We reviewed the literature to quantify the effect of metformin treatment on glycated hemoglobin (HbA(1c)) levels in all types of diabetes and examine the impact of differing doses on glycemic control.<h4>Research design and methods</h4>MEDLINE, EMBASE, and the Cochrane Library were searched from 1950 to June 2010 for trials of at least 12 weeks' duration in which diabe ...[more]

PMID: 22275444

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Project description:IntroductionMetformin has dose-dependent hypoglycemic effects on patients with type 2 diabetes (T2D). In Japan, metformin has been prescribed at lower doses than in Western countries. We analyzed the effect of increasing the metformin dose on glycemic control and compared it to a combination therapy with dipeptidyl peptidase-4 inhibitors (DPP-4i) and a replacement therapy with DPP-4i.MethodsThis is a cohort study using a Japanese claims database. Patients with T2D who had been initially treated with low-dose metformin (≥ 500 mg/day and < 1000 mg/day) and then given a prescription change by increasing metformin to a higher dose (≥ 1000 mg/day) (increased-dose), adding DPP-4i (drug-added), or switching to DPP-4i (drug-switched) were included in this study. The primary outcome was the change in HbA1c levels at 12 months from the baseline period.ResultsAmong 2,726,437 patients with T2D, 494 were included. Of these patients, 226, 240, and 28 patients were classified as increased-dose, drug-added, and drug-switched groups, respectively. The HbA1c levels at 12 months from the index significantly decreased compared to that during the baseline period. The change was the highest in the drug-added group (- 1.06%), followed by the increased-dose (- 0.91%) and the drug-switched groups (- 0.37%). Among the subset of patients who did not receive any antidiabetic drugs other than metformin or DPP-4i, the highest change in HbA1c levels was observed in the increased-dose group (- 0.84%), followed by the drug-added (- 0.67%) and the drug-switched (- 0.42%) groups. The order of decrease from baseline remained the same for all the study groups after the propensity score weighting adjustment.ConclusionThe effect on glycemic control when increasing the metformin dose was studied in patients who had been receiving low-dose metformin. Increasing metformin dosage shows effectiveness and could be one of the next treatment options in patients who were prescribed low-dose metformin as the first-line treatment.

Project description:BackgroundAcarbose and repaglinide are widely used either by themselves or in combination with other medications. However, their efficacy in diabetes control has not been compared when used in combination with metformin.MethodsThe present study aimed to compare their effects on glycemic variability (GV) control when taken with metformin for type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. In this retrospective cohort study, T2DM patients who were treated with either acarbose-metformin or repaglinide-metformin combination were recruited. Either acarbose 100 mg or repaglinide 2 mg triple daily was taken for the subsequent 12 weeks in combination with metformin. Demographic data, biochemical data and 7-point glycemic self-monitoring conducted with capillary blood (SMBG) data were reviewed after one week and 12 weeks. The primary outcome including glucose control and changes in GV as well as other factors affecting GV and the incidence of hypoglycemia were also analyzed.ResultsOf the 305 T2DM patients enrolled, data from 273 subjects, 136 in the acarbose-metformin group (M+A) and 137 in the repaglinide-metformin group (M+R) were analyzed. Both regimens improved glycemic control at 12 weeks post commencement of new medications. GV, expressed as the mean amplitude of plasma glycemic excursions (MAGE, 5.0 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.1 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R), standard deviation of blood glucose (SDBG, 3.6 ± 1.3 vs. 2.0 ± 0.9 mmol/L, p < 0.001 in M+A; 3.7 ± 1.3 vs. 2.4 ± 1.3 p < 0.001 in M+R), coefficient of variation of blood glucose (CVBG, (0.30 ± 0.09 vs. 0.21 ± 0.1, p < 0.001 in M+A; 0.31 ± 0.09 vs. 0.24 ± 0.12, p < 0.001 in M+R), postprandial amplitude of glycemic excursions (PPGE, 5.2 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.3 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R) or largest amplitude of glycemic excursions (LAGE, 9.8 ± 3.6 vs. 5.4 ± 2.4 mmol/L, p < 0.001 in M+A; 10.1 ± 3.4 vs. 6.3 ± 3.2 mmol/L, p < 0.001 in M+R) decreased significantly after the addition of acarbose or repaglinide (p < 0.05 respectively). Compared with repaglinide-metformin, acarbose-metformin was more effective in GV control at 12 weeks post commencement of new medications (p < 0.05). This study indicates that both acarbose-metformin and repaglinide-metformin combinations could effectively reduce GV and the acarbose-metformin combination seems to be more effective than the repaglinide-metformin combination. However, this conclusion should be confirmed by future large-scaled and more comprehensive studies due to the limitations of the present study.

Project description:BackgroundImpaired insulin activity in women with polycystic ovary syndrome might differ from that seen in type 2 diabetes mellitus without polycystic ovary syndrome. This study was designed to compare the effects of treatment with metformin, saxagliptin, and their combination in newly diagnosed women with type 2 diabetes mellitus and polycystic ovary syndrome in China.MethodsA total of 75 newly diagnosed patients from Shanghai, China with type 2 diabetes mellitus and polycystic ovary syndrome were included in this randomized, parallel, open-label study. All patients received treatment for 24 weeks with metformin, saxagliptin, or their combination. Patients were allocated to one of three treatment groups by a computer-generated code that facilitated equal patient distribution of 25 patients per group. The primary outcome was a change in glycemic control and ?-cell function.ResultsA total of 63 patients completed the study (n?=?21, for each group). The reduction in hemoglobin A1c was significant in the combination group, compared to the monotherapy groups (saxagliptin vs. combination treatment vs. metformin: -?1.1 vs. -1.3 vs. -1.1%, P?=?0.016), whereas it was comparable between the metformin and saxagliptin groups (P?>?0.05). Saxagliptin, metformin, and the combination treatment significantly reduced the homeostasis model assessment- insulin resistance index and increased the deposition index (P?<?0.01 for all). However, no significant change was observed in the homeostasis model assessment- ?-cell function among the metformin and combination groups, and no significant changes were observed in the insulinogenic index among all three groups (P?>?0.05 for all). In addition, saxagliptin and metformin treatments significantly reduced body mass index and high-sensitivity C-reactive protein levels (P?<?0.01 for both).ConclusionsSaxagliptin and metformin were comparably effective in regulating weight loss, glycemic control, and ?-cell function, improving lipid profiles, and reducing inflammation in newly diagnosed type 2 diabetes mellitus patients with polycystic ovary syndrome.Trial registrationChiCTR-IPR-17011120 (retrospectively registered on 2017-04-12).

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Quantifying the effect of metformin treatment and dose on glycemic control.

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Quantifying the effect of metformin treatment and dose on glycemic control.

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