L Pooled analysis of abdominal pain. M Pooled analysis of any cause of death. Indirectness of evidence was downgraded for any adverse events, any adverse events leading to discontinuation, severe adverse events, change in HbA1c, postprandial blood glucose, and FPG due to the indirectness of composite outcomes or surrogate outcomes.
Three of the included RCTs investigated patient compliance to treatment. Quantitative analysis of these assessments was not performed because of heterogeneity in the measurements.
In an RCT conducted in patients in , one patient in the metformin XR group discontinued treatment because of noncompliance, whereas no patients discontinued in the metformin IR group Aggarwal et al. An RCT conducted in reported that Another RCT conducted in reported that of None of the included studies compared patient satisfaction with metformin XR vs.
Our systematic review did not identify clear differences in the effectiveness and safety of metformin XR vs. To the best of our knowledge, this is the first systematic review to compare the IR and XR preparations of metformin.
Although both metformin IR and XR are widely used in clinical practice, the rationale for choosing one formulation over the other has not been widely examined. Guidance on the differential use of metformin XR vs. IR is largely absent in clinical practice guidelines for diabetes treatment, with the exception of the NICE guideline, which recommends the use of metformin XR in patients intolerant to metformin IR McGuire et al.
However, the NICE guideline recommendation is not supported by any specific evidence. Although the findings of some previous studies are in alignment with the NICE recommendation, the results from those studies are not conclusive Derosa et al.
In one such RCT, a reduced risk of gastrointestinal intolerance was observed with metformin XR treatment. Although the glucose-lowering effect of metformin XR was inferior to that of metformin IR, the results of this trial, in which the ratio of the glucose level decrease to the mean serum level of metformin was calculated, indicate the superior efficacy of metformin XR Henry et al. A study conducted in Italy also supported the superior glucose-lowering effect of metformin XR at the maximal tolerated dose compared with metformin IR Derosa et al.
However, the data from these trials did not clarify whether the superior tolerance observed for metformin XR was attributable to the lower dose. Neither of these trials was included in our systematic review because both featured different doses of metformin XR and IR between the treatment arms. Our findings support similar effectiveness and safety of metformin XR and IR, indicating that it might not be appropriate to switch from metformin IR to metformin XR for the purpose of improving glucose control or reducing adverse events.
Our results highlight the need for a change in clinical practice with respect to the selection of metformin preparation. Our findings also indicate better compliance with metformin XR treatment due to its once-daily dosing regimen.
The results were consistent across the included randomized trials and observational studies, regardless of the population heterogeneity compared with real-world practice Zhou et al. We inferred that as the number of doses increases, patients are increasingly likely to miss a dose, leading to noncompliance Godman et al.
This observation is not unique to metformin therapy in diabetes but is also observed in the treatment of other chronic diseases Shahiwala, A meta-analysis indicated that once-daily administration of antibiotics was associated with better compliance than twice- or thrice-daily treatment Falagas et al.
Another meta-analysis of antiviral treatment of HIV reported that compliance to a once-daily regimen was slightly better than that to a twice-daily regimen Nachega et al. Further, a pilot study among patients reported that once-daily dosage regimens were largely preferred by patients Witticke et al. Therefore, clinicians should consider patient preference when deciding on the type of formulation to prescribe and should consider metformin XR for patients who prefer once-daily dosing.
The selection of metformin preparation thus represents a good example of patient-centered care, where shared decision-making can be beneficial. Clinicians should also consider which patients will benefit most from once-daily administration. For example, adults in full-time employment may benefit from less frequent dosing, while it may not be necessary to prescribe metformin XR to patients with polypharmacy.
Our previous survey study indicated that most outpatients in China did not have an accurate understanding of why they were receiving the XR formulation of metformin Liu et al.
The majority This finding when considered alongside the results of the current systematic review is indicative of shortcomings in the dissemination of evidence to the patients and, potentially, to clinicians. The findings of our systematic review support the education of patients regarding the use of antidiabetic medications.
Our study had some limitations. First, we included only five randomized trials and one observational study; however, the overall sample size of more than 10, patients supported the robustness of our results. Second, long-term endpoints were not identified for metformin XR and IR use. Further long-term observational studies are needed to confirm the present findings. In conclusion, although metformin XR and IR formulations have similar effectiveness and safety, metformin XR is associated with increased treatment compliance.
These findings require dissemination to patients and clinicians, and long-term observation of the use of these two formulations is warranted. SL conceived this study. JT and YW performed the literature search, screening, and data extraction. All authors contributed to data analysis and drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Aggarwal, N. Diabetes Obes. Amod, A. Diabetes South Africa 17, 61— Blonde, L. Derosa, G. Dddt 11, — Donnelly, L. Falagas, M. PLoS One 10 1 , e Foretz, M. Metformin: from Mechanisms of Action to Therapies. Cel Metab. Fujioka, K. Gao, H. Godman, B. Expert Rev. Pharmacoeconomics Outcomes Res. Epub Apr 1. Guyatt, G. BMJ , — Hameed, M. Ayub Med. Abbottabad 29 2 , — PubMed Abstract Google Scholar.
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Expert Opin. Drug Deliv. Sun, X. Type 2 diabetes mellitus is diagnosed when the body becomes resistant to the effects of insulin. When the body cannot use insulin properly, blood sugar levels rise which can cause damage to the blood vessels and nerves. Without proper treatment, diabetes can lead to complications and damage to organs such as the heart and kidneys. Metformin is available in an immediate-release IR and extended-release ER form.
While both forms of metformin contain the same active ingredient, they are taken in different ways. They also have some differences in side effects.
Metformin or metformin hydrochloride is the generic name for Glucophage. Immediate-release metformin is usually dosed as a mg tablet taken twice daily with food. There is also an mg tablet that can be taken once daily.
The maximum dose of metformin is mg per day in divided doses. Metformin can treat type 2 diabetes in both adults and children. It is the extended-release version of metformin and only needs to be taken once daily with food. The maximum total daily dose of metformin ER is mg. Unlike immediate-release metformin, metformin ER is only indicated for adults with type 2 diabetes. It also has fewer side effects and lasts longer than regular metformin. Metformin can help improve glycemic control and ultimately prevent complications that can arise from diabetes.
Not only can metformin be used to treat type 2 diabetes, but it can also be used for off-label purposes. Those with prediabetes and a high fasting plasma glucose FPG may be recommended metformin to prevent the onset of diabetes. Metformin is recommended when blood sugar levels are not managed with diet and exercise alone. Metformin can also be used as an off-label option to treat gestational diabetes mellitus. This type of diabetes occurs in pregnant women who are predisposed to having diabetes.
However, insulin is usually tried first. Metformin has also been studied to treat polycystic ovary syndrome POCS. This syndrome is characterized by an imbalance of sex hormones which can result in ovarian cysts, menstrual cycle changes, pregnancy issues, acne, and insulin resistance. Metformin can be prescribed to help decrease insulin resistance, decrease testosterone levels, and improve menstrual cycles as well as fertility.
The use of antipsychotic medications, such as olanzapine , risperidone , and clozapine , can lead to weight gain. According to some studies, Metformin has been shown to be effective for treating antipsychotic-induced weight gain. One review found that metformin helped reduce body mass index BMI , body weight, and insulin resistance compared to placebo in those with antipsychotic-induced weight gain.
Based on studies comparing metformin and metformin ER for type 2 diabetes mellitus, metformin ER has been found to be comparable to metformin in effectiveness. In fact, metformin ER may be superior to regular metformin based on its lower side-effects profile and ease of use. Those with type 2 diabetes mellitus may be more inclined to take a once-daily metformin pill instead of a twice-daily pill.
In one randomized, clinical study , metformin ER was found to be more effective than metformin IR when treating patients with type 2 diabetes. Those taking metformin ER experienced better glycemic control and lipid metabolism compared to metformin IR. Another randomized, double-blind trial found that once-daily metformin ER had similar efficacy and safety to regular metformin. Additionally, the study noted an advantage of once-daily dosing with metformin ER. Both metformin and metformin ER improved HbA1c levels over 24 weeks in subjects who had never tried any other treatment for their diabetes.
Extended-release metformin may be preferred over immediate-release metformin. It has been shown to have better tolerability although it may be more expensive than immediate-release tablets. Metformin is the generic version of Glucophage. Generic metformin is covered by Medicare part D and most insurance plans. This cost can be reduced by bringing a SingleCare discount card to the pharmacy.
Almost all Medicare and insurance plans will cover generic metformin ER. Even with insurance, SingleCare may be able to offer a lower price. Check with your pharmacy to see if you can take advantage of a better discount with SingleCare.
Get the SingleCare prescription discount card. Metformin causes side effects that affect the gastrointestinal GI system. These side effects include diarrhea, nausea, vomiting, gas flatulence , indigestion, and abdominal discomfort or stomach upset.
Metformin IR also commonly causes fatigue or lack of energy asthenia as well as headaches. Metformin ER has fewer side effects compared to metformin. The most common side effects associated with metformin ER are diarrhea, nausea, and vomiting. Metformin ER can also cause constipation in some people. Although metformin ER can cause other GI side effects such as indigestion and flatulence, these side effects do not occur as often compared to regular metformin.
Other side effects that can occur with metformin and metformin ER include dizziness, lightheadedness, and taste disturbances. Other more serious side effects of metformin and metformin ER include liver injury and hypoglycemia low blood sugar.
This may not be a complete list. Consult your doctor or pharmacist for possible side effects. Metformin and metformin ER can interact with several different medications.
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