Pharmacotherapy of Type 2 Diabetes Mellitus: An Update on Drug–Drug Interactions

Amin, Muhammad; Suksomboon, Naeti

doi:10.1007/s40264-014-0223-2

Cited by 25 publications

(32 citation statements)

References 105 publications

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“…Third, the increase in GIB/ICH rate with concomitant use of warfarin and fenofibrate was delayed, and interactions involving enzymatic inhibition are usually rapid-onset interactions. [70] This apparent drug interaction is also unlikely mediated by protein binding displacement. Such interactions are generally considered transient because the increased amount of unbound drug is readily metabolized or eliminated.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Leonard

Brensinger

Bilker

et al. 2017

International Journal of Cardiology

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Background Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. Methods The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999–2011. Exposure was defined by concomitant use of warfarin plus one of eight antihyperlipidemics. The primary outcome measure was a composite of GIB/ICH within the first 30 days of concomitant use. As a secondary outcome measure, GIB/ICH was examined within the first 180 days of concomitant use. Results Among 236,691 persons newly-exposed to warfarin and an antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence interval 12.7 to 13.8) per 100 person-years. Users were predominantly older, female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual statins were consistent with no association. Warfarin + gemfibrozil was associated with an 80% increased risk of GIB/ICH within the first month of concomitant use (aHR = 1.8, 1.4 to 2.4). Warfarin + fenofibrate was associated with a similar increased risk (aHR = 1.8, 1.2 to 2.7), yet with an onset during the second month of concomitant use. Conclusions Among warfarin-treated persons, the use of fibrates—but not statins—increases the risk of hospital presentation for GIB/ICH.

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Section: Discussionmentioning

confidence: 99%

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Leonard

Brensinger

Bilker

et al. 2017

International Journal of Cardiology

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“…First, concomitant use of rosuvastatin, an inhibitor of CYP2C9, was not associated with an increased rate of severe hypoglycemia. Second, the increases in hypoglycemia rate with concomitant use of fibrates were delayed, and interactions involving enzymatic inhibition are usually rapid‐onset interactions . Finally, there was a suggestion of an increased rate of severe hypoglycemia among users of metformin + fenofibrate, and metformin is not hepatically metabolized and only rarely causes hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…Managing drug–drug interactions is regarded as a cornerstone of antidiabetic therapy . By far the most important consequence of such interactions is severe hypoglycemia, an outcome of significant clinical and public health concern that is feared by patients and their relatives .…”

Section: Discussionmentioning

confidence: 99%

“…Second, the increases in hypoglycemia rate with concomitant use of fibrates were delayed, and interactions involving enzymatic inhibition are usually rapid-onset interactions. 23 Finally, there was a suggestion of an increased rate of severe hypoglycemia among users of metformin 1 fenofibrate, and metformin is not hepatically metabolized and only rarely causes hypoglycemia. Future work should elucidate the mechanism(s) underlying this apparent drug interaction.…”

Section: Discussionmentioning

confidence: 99%

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Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics

Leonard

Bilker

Brensinger

et al. 2016

Clin Pharma and Therapeutics

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Background Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. Methods We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Results Among 592,872 persons newly-exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24–1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11–1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29–2.06) for glimepiride+fenofibrate. Conclusions Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.

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“…SUs are associated with moderate glycemic efficacy, although these agents are recommended for patients with a disease duration of less than 5 years55 because the mechanism of action is dependent on functioning β-cells 53. In addition, because SUs act independently of plasma glucose concentrations, the main risk is hypoglycemia, which may be exacerbated by coadministration with other drugs, especially those that inhibit SU metabolism via the cytochrome P450 2C9 isozyme 79. To avoid hypoglycemia, the addition of a DPP-4 inhibitor or a GLP-1RA to metformin may be considered instead.…”

Section: Potential Combinations To Improve Pathophysiologic Dysfunctionmentioning

confidence: 99%

Practical combination therapy based on pathophysiology of type 2 diabetes

Levin

2016

DMSO

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Type 2 diabetes is a complex, chronic, and progressive condition that often necessitates the use of multiple medications to achieve glycemic goals. Clinical guidelines generally recommend intensifying pharmacotherapy if glycemic goals are not achieved after 3 months of treatment. However, for many patients with type 2 diabetes, treatment intensification is delayed or does not occur. Initiating combination therapy early in the disease course has the potential to delay disease progression and improve patient outcomes. Guidelines generally provide a list of agents that may be used in combination regimens and emphasize individualization of treatment. The purpose of this review is to discuss the rationale for combination therapy, considering treatment effects on pathophysiologic aspects of type 2 diabetes and individual drug profiles. The combination of newer antidiabetes therapies with complementary mechanisms of action provides the opportunity to target multiple sites of tissue, organ, and cellular dysfunction.

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Pharmacotherapy of Type 2 Diabetes Mellitus: An Update on Drug–Drug Interactions

Cited by 25 publications

References 105 publications

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics

Practical combination therapy based on pathophysiology of type 2 diabetes

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