Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes

Belcher, G.; Lambert, Ceri; Edwards, G.; Urquhart, Richard; Matthews, David R.

doi:10.1016/j.diabres.2005.02.011

Cited by 73 publications

(41 citation statements)

References 25 publications

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“…An increase in insulin-sensitive sodium retention with secondary fluid retention may also occur. 28 The mean weight gain observed in our patients was the same as reported in other trials. 5,25 Additionally, our study showed that weight gain was proportional to improved glycaemic control which was again consistent with previous studies.…”

Section: Discussionsupporting

confidence: 87%

Comparison of the effects of long-term pioglitazone and rosiglitazone therapy on liver enzymes in type 2 diabetes

Yeap

Lockman

Elton

et al. 2011

Diabetes & Vascular Disease

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AimsInsulin resistance is a major factor influencing the progression of non-alcoholic fatty liver disease (NAFLD). Hence, insulin sensitisers such as thiazolidinediones (TZDs) are a potential treatment for NAFLD although their long-term benefits remain unknown. MethodsWe retrospectively studied 396 and 364 type 2 diabetes patients who received pioglitazone and rosiglitazone therapy respectively from diabetes clinics between May 2001 and November 2007. ResultsOne hundred and seventy-seven pioglitazone-treated and 152 rosiglitazone-treated patients were included. After a year of treatment, significant improvement in glycated haemoglobin A 1C (HbA 1C ), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) was observed in both groups despite weight gain. Changes in HbA 1C and liver function test (LFT) were positively correlated in pioglitazone-treated (ALT p=0.01; GGT p<0.001; ALP p=0.006) and rosiglitazone-treated (GGT p=0.01, ALP p=0.002) groups. Multiple regression showed no significant difference in the changes in ALT (p=0.43) and GGT (p=0.13) between the groups but a larger reduction in ALP (p=0.03) was noted in rosiglitazone-treated patients. Sixty patients remained on pioglitazone and 46 patients continued on rosiglitazone after four years. Sustained improvement in ALT, GGT and HbA 1C was observed in both groups despite weight gain over four years. ConclusionsFour years of TZD therapy resulted in sustained improvement in LFT despite weight gain. Br J Diabetes Vasc Dis 2011;11:121-129.

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Section: Discussionsupporting

confidence: 87%

Comparison of the effects of long-term pioglitazone and rosiglitazone therapy on liver enzymes in type 2 diabetes

Yeap

Lockman

Elton

et al. 2011

Diabetes & Vascular Disease

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“…16,17 Long-term treatment with either agent is a possibility as both are well tolerated and safe; minor common side effects being peripheral edema with pioglitazone, and diarrhea and abdominal upset with metformin. 18 However, the ability to maintain a long-term response will need to be shown. Indeed, in the case of metformin improvements in serum aminotransferase levels and hepatic histology may not be sustained for even 48 weeks despite continuation of the medication.…”

Section: Discussionmentioning

confidence: 99%

The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis

et al. 2007

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A pilot study of a 48-week course of pioglitazone demonstrated significant improvements in the biochemical and histological features of nonalcoholic steatohepatitis (NASH). The aim of the study was to assess the effects of stopping pioglitazone. Twenty-one patients with NASH were treated with pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment evaluation including liver biopsy. Thirteen patients were followed for at least 48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical comparisons were made to evaluate whether discontinuation of pioglitazone resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was associated with subsequent elevation in serum alanine aminotransferase levels (from 34 ؎ 13 to 70 ؎ 39 IU/l), decrease in adiponectin (from 9.7 ؎ 9.1 to 5.1 ؎ 4.5 g/ml), worsening insulin sensitivity (HOMA Index: from 2.9 ؎ 1.8 to 5.5 ؎ 5.4), and increase in total hepatic fat (from 30% ؎ 32% to 71% ؎ 33%) despite no change in average body weight compared to the end of treatment. Repeat liver biopsy in 9 patients revealed significant worsening of parenchymal inflammation (from 1.2 ؎ 0.7 to 2.9 ؎ 1.1) and steatosis (from 0.9 ؎ 0.6 to 2.1 ؎ 1.3) but no change in fibrosis (from 1.1 ؎ 1.2 to 1.2 ؎ 1.3). NASH was again present on liver biopsy in 7 patients. Conclusion: These findings suggest that long-term therapy with pioglitazone may be necessary to maintain improvements in disease activity in patients with NASH, although weight gain during treatment may ultimately limit its beneficial effects. (HEPATOLOGY 2007;46: 424-429.)See Editorial on Page 285 N onalcoholic steatohepatitis (NASH) is an inflammatory liver disease associated with progressive liver injury which can eventually lead to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. 1 The etiology of NASH is thought to be related to insulin resistance and the metabolic syndrome. 2 NASH is closely associated with obesity and thus may represent the most prevalent chronic liver disease in the United States. 3,4 Several strategies aimed at improving insulin resistance have been employed in clinical trials for NASH, one being controlled weight loss using diet and exercise. This approach has had limited success in those patients who are able to lose and maintain weight loss in the long term. The improvement in histology with weight loss is primarily in hepatic steatosis rather than inflammation and fibrosis. [5][6][7] Thus far, pharmacological therapy aimed at weight loss has been disappointing, and histological data on the effects of weight-loss medications are lacking. 8 A more sustained option is bariatric surgery which has been shown to promote marked weight loss, decrease insulin resistance, and improve liver histology in patients with NASH. 9 However, for most patients with NASH, an invasive surgical procedure with major metabolic effects is not an appropriate option.Drug therapy primarily aimed at improving insulin resistance presents a possible option for patien...

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“…8,9) In the present study, we initially clarified the incidence and profiles of ADRs caused by initial treatment of metformin in patients hospitalized with T2DM patients. Secondly, we aimed to identify risk-factors related to ADR(s) to encourage the appropriate use of metformin.…”

mentioning

confidence: 99%

The Evaluation of Risk Factors Associated with Adverse Drug Reactions by Metformin in Type 2 Diabetes Mellitus

Okayasu

Kitaichi

Hori

et al. 2012

Biological & Pharmaceutical Bulletin

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Metformin is a drug to improve glycemic control by reducing insulin resistance and is currently considered to be one of the first-choice drugs for type 2 diabetes mellitus (T2DM). However, during metformin use, adverse drug reactions (ADRs) including gastrointestinal adverse events were frequently observed. Thus, in the present study, we investigated the incidence of ADRs induced by metformin and further analyzed risk factors for ADRs in Japanese patients with type 2 diabetes mellitus who initially administered metformin (500-750 mg). One hundred and one hospitalized patients receiving metformin during September 1, 2009 and August 31, 2010 were studied. The incidence of ADRs and changes in laboratory data including hemoglobin A1c (HbA1c) were monitored retrospectively. The anti-glycemic effect of metformin was successfully observed as indicated by decreased HbA1c. Among ADRs, diarrhea was most frequently occurred during metformin use (26.7% of patients) although the symptom of diarrhea was mild in most cases and disappeared within 3 d after the initial use. A logistic regression analysis showed the existence of six risk factors, including initial dose (750 mg), female, age (≦65), body mass index (≧25), aspartate aminotransferase (≧30 IU/L) and alkaline phosphatase (≧270 IU/L). The incidence of diarrhea increased linearly as the number of risk factors increased. In conclusion, in order to avoid ADRs, especially diarrhea, subsequently improving the quality of life during metformin use, the optimization of the dose of metformin by considering risk factors would be beneficial for patients with T2DM.

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Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes

Cited by 73 publications

References 25 publications

Comparison of the effects of long-term pioglitazone and rosiglitazone therapy on liver enzymes in type 2 diabetes

Comparison of the effects of long-term pioglitazone and rosiglitazone therapy on liver enzymes in type 2 diabetes

The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis

The Evaluation of Risk Factors Associated with Adverse Drug Reactions by Metformin in Type 2 Diabetes Mellitus

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