Metformin observational studies

Masoudi FA, Inzucchi SE, Wang Y, et al. Thiazolidine-diones, metformin, and outcomes in older patients with diabetes and heart failure an observational study. Circulation. Feb 8 2005 lll(5) 583-590. 

Olsson J, Lindberg G, Gottsater M, Lindwall K, Sjostrand A, Tisell A, Melander A. Increased mortality in Type II diabetic patients using sulphonylurea and metformin in combination a population-based observational study. Diabetologia 2000 43(5) 558-60. 

In the metformin monotherapy cohort 4.7% of patients died (35.5% cardiovascular deaths), compared with 17.9% of patients in the SU monotherapy cohort (42.4% cardiovascular deaths). After adjusting for aU available confounders, the risk for mortality and cardiovascular mortality in patients in the SU only cohort remained significantly increased with 1.43 and 1.70, respectively compared to the metformin monotherapy. Patients in the combination cohorts had significantly increased risk of mortality (2.47 and 2.16) and cardiovascular mortality (2.29 and 2.43) despite the adjustment for all available confounders and irrespective whether the patients started either with sulfonylureas or metformin and then added the other drug. A significantly reduced risk for overall mortality [odds ratio (OR) = 0.60] and cardiovascular mortahty was already earher observed in a Canadian observational study [37] of 1,150 users of metformin therapy in comparison with 3,033 users of sulfonylureas. By contrast, in that study sulfonylurea plus metformin combination therapy was also associated with reduced all-cause mortality (OR = 0.66). 

Prospective controlled studies about the use of metformin in diabetic patients after acute myocardial infarction or heart failure are not available. Indirect information is coming from several large observational studies. In a retrospective cohort study of 24,953 diabetic patients [38] discharged after hospitalization with acute myocardial infarction, mortality rates after 1 year were not significantly different in patients treated with either metformin [Hazard ratio (HR) = 0.92] or a thia-zolidendione (0.92) in comparison with patients who did not receive an insulin sensitizer but were lower in those prescribed both drugs (0.52). 

Similar observations were made in a case-conholled study from Scotland [42] suggesting that the use of metformin may be associated with reduced risk of cancer (HR = 0.79). In Une with these observational studies are new experimental data [43] demonshating that metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. 

Tumorigenicity Type 2 diabetes and use of insulin is a well-established risk factor for the development of malignancy. [S l One of the largest observational studies so far identified more than 60,000 diabetic patients and showed that patients on insulin were more likely to develop solid tumours than those on metformin with an adjusted hazard ratio (HR), 1.08 (95% confidence interval Cl 0.96-1.21) for metformin plus sulphonylurea, 1.36 (95% Cl 1.19-1.54) for sulphonylurea monotiierapy, and 1.42 (95% Cl 1.27-1.60) for insulin-based regimens,... 

In a recent 36-weeks study glargine or NPH insulin were combined with metformin [21], HbAlc decreased similar values in the two groups, but the incidence of hypoglycaemia was lower in the glargine group the first 12 weeks of treatment. Thereafter, no difference was observed between the two treatments. 

Lastly, Barnett et al. in a 24-week study randomised type 2 patients uncontrolled on sulfonylurea monotherapy to inhaled insulin before meals or metformin and demonstrated in subjects with HbAlc >9.5% at randomisation a greater reduction in HbAlc in the inhaled insulin-treated group (2.2% vs. 1.8%) [62]. In the patients with HbAlc <9.5% at randomisation, the decrease in HbAlc was not different between the two groups. More events of hypoglycaemia were observed in the inhaled insulin group [62]. 

Carboxymethyl gellan gum Metformin HCl lonotropically gelled beads Studies showed ex-vivo bioadhesion of 100% over 24 h and it was observed that carboxymethyl gellan gum beads released metformin at a rate faster than gellan gum. [71]... 

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