Safety, Efficacy, and Bioavailability of Fixed-Dose Combinations in Type 2 Diabetes Mellitus: A Systematic Updated Review

Abstract

PurposeType 2 diabetes mellitus (T2DM) is a multifactorial disease characterized by insulin resistance. As time progresses, monotherapy often does not provide effective glycemic control, generating the need for an add-on therapy. Hence, multiple oral hypoglycemic agents formulated as a single-dose form called fixed-dose combinations (FDCs) play an essential role in glycemic control. The purpose of this systematic review is to appraise the recently published evidence on the safety, efficacy, and bioavailability of FDCs.MethodsA comprehensive literature search of PUBMED, Scopus, ScienceDirect.com, ProQuest, SpringerLink, clintrials.gov, Embase, and EBSCO using the key words FDCs, combination therapy, T2DM management, and add-on therapy was conducted. Studies on the safety profile/tolerability, efficacy, and bioavailability of various FDCs of oral hypoglycemic agents were preferred.FindingsThe systematic review of all the publications suggests that FDCs of oral hypoglycemic agents (OHAs) significantly reduce HbA1c and fasting plasma glucose values, thereby efficiently reducing hyperglycemia in patients in whom monotherapy fails. FDCs are the bioequivalent of the concomitant drugs administered as individual components. Improved adherence to FDCs and the absence of serious adverse drug reactions compared with dual therapy play an important role in decreasing the incidence of hyperglycemia in patients with T2DM.ImplicationsFrom this updated review, it was found that metformin was the most widely used component of FDCs with other OHAs. Studies on the safety and efficacy of newly approved OHAs such as sodium glucose cotransporter inhibitors were limited. An increasing number of randomized trials on the safety and efficacy of newly emerging FDCs suggests that they would be better treatment options for T2DM patients.

Iraqi Experts Consensus on the Management of Type 2 Diabetes/Prediabetes in Adults

“…Available studies support the wider use of FDC in the treatment of T2DM patients and the efficacy and safety of newer FDC seems to be promising and adds more treatment options. 43,44 The panel highlighted that, when prescribing and choosing the dual therapy option, the physician should consider drugspecific effect and patient factors. Atherosclerotic cardiovascular patients should take in combination to diabetic therapy a medication shown to reduce cardiovascular risks, two different SUs should not be combined, DPP-4i should not be combined with GLP-1RA and the insulin secretagogues such as SUs and meglitinides should be discontinued once insulin is introduced into a treatment regimen or at least within few months.…”

Fixed‐dose combination of amlodipine and atorvastatin improves clinical outcomes in patients with concomitant hypertension and dyslipidemia

“…Furthermore, nonadherence was also confirmed as an important contributor to the higher hospitalization rate and health care cost 20 . Currently, FDC is widely used in several chronic diseases such as hypertension, DM, and pulmonary tuberculosis to simplify treatment regimens, improving medication adherence and clinical outcomes 10,12,21‐24 . In our previous study, compared to the free combination of CCB/ARB, the FDC of amlodipine/valsartan improves MACE‐free survival, medication compliance, hospitalization rates, and also decreases total health care costs 12 .…”

“…In our previous study, compared to the free combination of CCB/ARB, the FDC of amlodipine/valsartan improves MACE‐free survival, medication compliance, hospitalization rates, and also decreases total health care costs 12 . The effect of FDC in the treatment of type 2 DM has been addressed in a systemic review including 10 studies, 2 of which were prospective, 1 was observational, and 7 were randomized, double‐blinded, parallel studies 21 . The authors concluded that the FDCs of various oral hypoglycemic agents significantly reduce glycated hemoglobin and fasting plasma glucose values, improve adherence, and reduce serious adverse drug reactions in diabetic patients.…”

Prescribing Trends and Rationality of Fixed Dose Combinations in a Tertiary Care Hospital: An Observational Study

“…The dosing schedule of individual constituent of FDCs may differ and this may result in inflexible dosing regimen. There may be interaction among constituents of FDCs and this may result in adverse effects, particularly when drugs belonging to the same pharmacological class are used [4][5][6] . The increased number of prescriptions with FDCs is a matter of concern as it may develop irrational prescribing patterns in hospitals.…”