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Metformin And Dpp 4 Combination

Combination Therapy With Sitagliptin And Metformin For Type 2 Diabetes

Combination Therapy With Sitagliptin And Metformin For Type 2 Diabetes

The two incretin hormones, glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide potentiate nutrient-dependent insulin secretion following meal ingestion. Metabolic control can be improved markedly by administration of exogenous GLP-1, but the native peptide is almost immediately degraded by the enzyme dipeptidyl peptidase (DPP)-4 and, therefore, has little clinical value. Oral formulations that inhibit DPP-4, thereby prolonging the duration of endogenous incretin action, have, therefore, been developed. Sitagliptin, a once-daily, orally active, competitive and fully reversible inhibitor of DPP-4, was, as first in its class, introduced to the market as Januvia. Recently, the US FDA approved initial combination therapy with sitagliptin and metformin (Janumet) in order to help more patients with Type 2 diabetes mellitus get closer to accepted glycemic control targets, as recommended by standard guidelines. This article reviews initial treatment with Janumet as an alternative to monotherapy. Type 2 diabetes mellitus (T2DM) has become a huge socioeconomic global burden over the last few decades and its prevalence is still increasing.[ 1 ] Patients with T2DM are characterized by multiple defects contributing to hyperglycemia, including inappropriate insulin secretion and insulin resistance.[ 2 , 3 ] Furthermore, patients with T2DM are also characterized by elevated fasting plasma glucagon concentrations that fail to decrease or, paradoxically, may even increase after carbohydrate ingestion, leading to excessive hepatic glucose production.[ 4 , 5 , 6 ] Thus, T2DM represents a complex disease and optimal treatment requires a multifaceted approach. Initial oral antidiabetic drugs (OADs) in monotherapy are often insufficient at getting patients to glyce Continue reading >>

Need An Add-on To Metformin? Consider This

Need An Add-on To Metformin? Consider This

Need an Add-on to Metformin? Consider This Clinician Reviews. 2017 February;27(2):20-22 David Wyncott is with the St. Joseph Health System Family Medicine Residency, Mishawaka, Indiana. Corey Lyon is with the University of Colorado Family Medicine Residency, Denver. Anne Mounsey is in the Department of Family Medicine at the University of North Carolina, Chapel Hill. Sulfonylureas have been the preferred add-on therapy to metformin for T2DM, but a study finds that DPP-4s have lower risks for death, CV events, and hypoglycemia. 1. Ou SM, Shih CJ, Chao PW, et al. Effects of clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Ann Intern Med. 2015;163:663-672. 2. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197-2206. 3. American Diabetes Association. Standards of Medical Care in Diabetes2016. Diabetes Care. 2016;39(suppl 1). 4. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm2016 Executive Summary. Endocr Pract. 2016;22: 84-113. 5. Phung OJ, Scholle JM, Talwar M, et al. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010;303:1410-1418. 6. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475-483. 7. Scirica BM, Bhatt DL, Brau Continue reading >>

Novel Combination Treatment Of Type 2 Diabetes Dpp-4 Inhibition + Metformin

Novel Combination Treatment Of Type 2 Diabetes Dpp-4 Inhibition + Metformin

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin Bo Ahrn, Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden; Correspondence: Bo Ahrn Department of Clinical Sciences, Division of Medicine, Lund University, B11 BMC, SE-221 84 LUND, Sweden Tel +46462220758 Email [email protected] Copyright 2008 Dove Medical Press Limited. All rights reserved This article has been cited by other articles in PMC. Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1(GLP-1). Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis) and sitagliptin (JanuviaR, Merck). These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1c levels by 0.65%1.1% (baseline HbA1c 7.28.7%) in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1c was reduced by this combination by 2.1% (baseline HbA1c 8.8%) after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with Continue reading >>

Dpp-4/sglt2 Inhibitor Combined Therapy For Type 2 Diabetes

Dpp-4/sglt2 Inhibitor Combined Therapy For Type 2 Diabetes

DPP-4/SGLT2 inhibitor combined therapy for type 2 diabetes Steve Chaplin November 13, 2017 28.11 November 2017 DPP-4 inhibitors and SGLT2 inhibitors lower blood glucose by complementary mechanisms of action, and two fixed-dose combinations Qtern and Glyxambi have now been approved for the treatment of type 2 diabetes. This article discusses their clinical trial efficacy, adverse effects and place in therapy. The treatment of type 2 diabetes has undergone radical change since the introduction of drugs that modulate incretin the glucagon-like peptide-1 (GLP-1) receptor agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. These agents expanded the options available before and after prescribing insulin and, compared with the sulfonylureas, they have a low risk of hypoglycaemia. The DPP-4 inhibitors in particular have achieved remarkable success: in 2016/17, they were, only 10 years after their introduction, the most frequently prescribed other antidiabetic drug in primary care in England.1 (But, with 4.6 million items dispensed in that year, they lagged behind the 8.4 million items for sulfonylureas, a fact that probably reflects conservative treatment guidelines.) Sitagliptin has the lions share of DPP-4 inhibitor prescribing (56%), followed by linagliptin (27%) and saxagliptin (7%). The most significant development since then was the introduction of the sodium-glucose co-transporter 2 (SGLT2) inhibitors in 2012/13, another new class of drug with a low risk of hypoglycaemia. The past year has seen volume growth at a rate comparable with that of the DPP-4 inhibitors, and dapagliflozin, the first SGLT2 inhibitor in class, is now prescribed at about one-quarter of the frequency of sitagliptin in primary care. Blessed with an unparalleled therapeutic choice for the mana Continue reading >>

Glucagon.com

Glucagon.com

DPP-4 compounds approved for the treatment of type 2 diabetes include Vildagliptin (Galvus) (LAF237) , Sitagliptin (Januvia), Saxagliptin and Linagliptin (Tradjenta) Alogliptin is approved in Japan. Januvia (Sitagliptin) was approved for the treatment of type 2 diabetes in the United States on Oct 17 2006, for use as monotherapy, or combination therapy, with either metformin or a thiazolidinedione. Subsequenly, multiple DPP4 inhibitors havebeen approved worldwide, including saxagliptin, linagliptin, alogliptin, vildagliptin, and other gliptins in Asian markets. Administration of the first generation Novartis compound 1-[[[2-[(5-cyanopyridin-2-yl)amino] ethyl]amino]acetyl]-2- cyano-(S)- pyrrolidine (NVP DPP728) over a 4 week period to 93 patients with Type 2 diabetes (mean HbA1c of 7.4%) reduced levels of plasma glucose, insulin, and HbA1c over the 4 week study period. See Inhibition of Dipeptidyl Peptidase IV Improves Metabolic Control Over a 4-Week Study Period in Type 2 Diabetes. Diabetes Care. 2002 May;25(5) :869-875 Is metformin an inhibitor of DPP-4? Patients receiving metformin have also been noted to exhibit additive glucose lowering benefits following institution of GLP-1 therapy. See Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes. Diabetes Care. 2001 Apr;24(4):720-5 . In a study of 10 obese non-diabetic male patients, metformin administration was associated with increased levels of circulating GLP-1 following oral glucose-loading, and in experiments using pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C, in the presence or absence of DPP-4. The authors of this study raised the possibility that metformin may inhibit Continue reading >>

On Combination Therapy Of Diabetes With Metformin And Dipeptidyl Peptidase Iv Inhibitors

On Combination Therapy Of Diabetes With Metformin And Dipeptidyl Peptidase Iv Inhibitors

On Combination Therapy of Diabetes With Metformin and Dipeptidyl Peptidase IV Inhibitors 1Department of Physiology, University of British Columbia, Vancouver, Canada Diabetes Care 2002 Aug; 25(8): 1490-1491. Recently, data were presented showing that metformin increased plasma active glucagon-like peptide (GLP)-1[736NH2] concentrations in obese nondiabetic male patients ( 1 ), and it was suggested that metformin was a direct dipeptidyl peptidase (DP) IV inhibitor. Contradiction of this hypothesis is simply found by examining the modes of action of metformin and of the DP IV inhibitors. Although the specific molecular target of metformin is still unknown, biguanides generally act to sensitize peripheral tissues to insulin action (particularly, skeletal muscle) and inhibit hepatic gluconeogenesis and glycogenolysis ( 2 , 3 , 4 ). In contrast, DP IV inhibitors act to enhance the insulin response to a meal, via preservation of intact bioactive incretins, GLP-1[736NH2] and GIP[142OH] ( 5 , 6 , 7 , 8 , 9 , 10 ). Notably, metformin does not improve glucose tolerance via an increase in circulating insulin levels, implicating different antidiabetic mechanisms for metformin and DP IV inhibitors. Unfortunately, Mannucci et al. ( 1 ) did not measure total GLP-1 (GLP-1[736NH2] + GLP-1[936NH2]) levels in their study. An increase NH2-terminal intact GLP-1 was interpreted as indicating protection from degradation by DP IV, and the possibility of an increase in total GLP-1 levels, yielding a proportional rise in intact GLP-1 concentrations, was not considered. This possibility is consistent with prior studies examining glucagon and GLP-1 levels after metformin treatment ( 11 , 12 , 13 ). A simplistic interpretation of these findings would be that metformin either enhances the glucose s Continue reading >>

Diabetes Drugs: Dpp-4 Inhibitors

Diabetes Drugs: Dpp-4 Inhibitors

Editors Note: This is the ninth post in our miniseries about diabetes drugs . Tune in on October 9 for the next installment. DPP-4 inhibitors, a relatively new class of drugs for Type 2 diabetes, were introduced in 2006. Sitagliptin (brand name Januvia), the first medicine in this class, was approved for the treatment of Type 2 diabetes in October 2006; in July 2009, a second DPP-4 inhibitor, saxagliptin (Onglyza) , was approved. These drugs are approved for use as additional therapy in people with Type 2 diabetes alone or in combination with metformin (brand name Glucophage and others), sulfonylureas (Diabinese, DiaBeta, Glynase, Micronase, Glucotrol, Glucotrol XL, Amaryl), and thiazolidinediones (Actos, Avandia). This very recent addition of a new class of drugs might seem like the result of the latest research, but in fact, the science behind DPP-4 inhibitors goes back to research started in the early 1900s. As I mentioned in my post on GLP-1 agonists , the hormone glucagon-like peptide-1, or GLP-1, has a profound effect on both stimulating the release of insulin from the pancreas and delaying stomach emptying. Unfortunately, it is active only for a very short time because it is broken down by an enzyme called dipeptidyl peptidase-4, or DPP-4. Blocking DPP-4 prolongs the effect of GLP-1, and hence enhances insulin secretion and the slowed emptying of the stomach. It is known that people with Type 2 diabetes have impaired GLP-1 secretion and elevated DPP-4 activity, so blocking DPP-4 could directly address some of the issues in people with diabetes. Since DPP-4 inhibitors enhance the bodys own ability to release insulin, they can only be used in the treatment of Type 2 diabetes. Of note, researchers have found that after certain types of gastrointestinal surgery to t Continue reading >>

Combination Therapy Of Metformin Plus Dipeptidyl Peptidase-4 Inhibitor Versus Metformin Plus Sulfonylurea And Their Association With A Decreased Risk Of Cardiovascular Disease In Type 2 Diabetes Mellitus Patients

Combination Therapy Of Metformin Plus Dipeptidyl Peptidase-4 Inhibitor Versus Metformin Plus Sulfonylurea And Their Association With A Decreased Risk Of Cardiovascular Disease In Type 2 Diabetes Mellitus Patients

As a global public health issue, type 2 diabetes mellitus (T2DM) affected approximately 347 million individuals worldwide in 2008, among whom 10% are adults. [1] With some association with microvascular and macrovascular morbidity and mortality, hyperglycemia has been targeted in the management of T2DM. [2] Moreover, patients with T2DM have a 2- to 4-fold higher risk of cardiovascular disease (CVD) and CVD mortality compared with patients without T2DM. [3] However, it has not been demonstrated by clinical trials that those with T2DM who have achieved normal glucose levels can lower their risk for cardiovascular events. In 2012, the American Diabetes Association and the European Association for the Study of Diabetes proposed that metformin monotherapy was the first-line glucose-lowering drug treatment, without contraindications. [4] Unfortunately, many patients on metformin monotherapy failed to meet or keep glycemic control for a long period. Based on the 2009 guidelines of the National Institute for Health and Care Excellence (NICE), it is necessary to add a sulfonylurea to metformin therapy as long as this is not contraindicated by factors such as obesity or risk of hypoglycemia; otherwise, a dipeptidyl peptidase-4 (DPP-4) inhibitor or thiazolidinedione can be added. After the release of these guidelines, however, a greater understanding of alternative agents has been observed. Nonetheless, the choice of an additional therapeutic agent remains complex because the agents have to be compared with regard to their efficacy and safety. Sulfonylureas have been the most widely used add-on to metformin therapy for several years, but they may increase cardiovascular risks. [5,6] In recent years, as a class of agents, DPP-4 inhibitors have been permitted to treat T2DM and to i Continue reading >>

Dipeptidyl Peptidase-4 Inhibitors As Add-on Therapy To Metformin

Dipeptidyl Peptidase-4 Inhibitors As Add-on Therapy To Metformin

Dipeptidyl Peptidase-4 Inhibitors as Add-on Therapy to Metformin European Endocrinology, 2007(2):60-62; DOI: Citation European Endocrinology, 2007(2):60-62; DOI: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucosedependent insulinotropic polypeptide (GIP) are released after food intake and stimulate insulin secretion in a glucose-dependent manner.1 GLP-1 also inhibits glucagon secretion2 and, as evident from animal studies, may increase -cell mass.3 GLP-1 also induces satiety and may reduce bodyweight.4 Therefore, GLP-1 has been developed as a novel treatment for type 2 diabetes.5 However, GLP-1 is rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).6 To overcome this problem, two strategies for GLP-1-based therapy have evolved.7 One strategy has been the development of DPP-4-resistant GLP-1 receptor agonists such as exenatide,8 which is approved in both the US and the EU for treatment of type 2 diabetes. The other strategy uses inhibition of DPP-4.9 The rationale for DPP-4 inhibition as a treatment for type 2 diabetes is that the inactivation of GLP-1 is prevented, which would increase and prolong the suprabasal levels of endogenously released active GLP-1.9 This in turn will increase insulin secretion and reduce glucagon secretion, and thereby lower glucose levels. The first study to show efficiency of DPP-4 inhibition in diabetic patients demonstrated that a DPP-4 inhibitor (NVP-DPP728) improved metabolic control in drug-nave type 2 diabetic patients treated over four weeks.10 At present, several DPP-4 inhibitors are in clinical development. Sitagliptin (Januvia, Merck Research Laboratories) and vildagliptin (Galvus; Novartis Biomedical Research Institutes) are those with the longest experience; sitagliptin has been approved by the US Food Continue reading >>

Sulphonylurea Compared To Dpp-4 Inhibitors In Combination With Metformin Carries Increased Risk Of Severe Hypoglycemia, Cardiovascular Events, And All-cause Mortality

Sulphonylurea Compared To Dpp-4 Inhibitors In Combination With Metformin Carries Increased Risk Of Severe Hypoglycemia, Cardiovascular Events, And All-cause Mortality

Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin+sulphonylurea or metformin+dipeptidyl peptidase-4 inhibitor (DPP-4i). All patients with T2D in Sweden who initiated second-line treatment with metformin+sulphonylurea or metformin+DPP-4i during 20062013 (n=40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results. Of 52,760 patients; 77% started metformin+SU and 23% metformin+DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.113.86); 1.17 (1.011.37); and 1.25 (1.021.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks. Metformin+SU treatment was associated with an increased risk of sub Continue reading >>

Combination Therapy With Dpp-4 And Sglt2 Inhibitors Safe And Effective

Combination Therapy With Dpp-4 And Sglt2 Inhibitors Safe And Effective

Combination Therapy with DPP-4 and SGLT2 Inhibitors Safe and Effective Various studies have investigated the safety and efficacy of combining different antihyperglycemic medications. With the wide range of choices available, though, it can be difficult to make sense of which combinations might work best, and for which patients. Arecent review has looked at this issue, particularly regarding combined therapy with the newer DPP-4 and SGLT2 inhibitors. The review included clinical trials with at least 200 patients, and focused on change in HbA1c from baseline after 24 or more weeks of treatment with combination antihyperglycemics. Included articles were limited to those published in English, and studies looking at medications with FDA approval. The review included 33 articles from the DPP-4 class and 24 from the SGLT2 inhibitor class. In general, the studies indicated that adding a DPP-4 or SGLT2 inhibitor as a second or third agent resulted in improved glycemic control, reductions in weight (or at least a neutral weight effect), and low rates of hypoglycemia, especially when combined with metformin. * Dual and triple therapy with a DPP-4 inhibitor, metformin and/or a thiazolidinedione (TZD) improved HbA1c compared to monotherapy, without markedly increased hypoglycemia. * No major safety concerns were found. * There was a tendency for increased hypoglycemia when combined with a sulfonylurea. * There was a tendency for weight increases associated with TZDs. * Dual and triple therapy with an SGLT2 inhibitor and metformin, a TZD, and/or a DPP-4 inhibitor improved HbA1c compared to monotherapy or active comparators, without markedly increased hypoglycemia. * There was a tendency toward hypoglycemia when combined with insulin or a sulfonylurea. The overall safety and tolerabi Continue reading >>

Novel Combination Treatment Of Type 2 Diabetes Dpp-4 Inhibition + Metformin

Novel Combination Treatment Of Type 2 Diabetes Dpp-4 Inhibition + Metformin

Novel combination treatment of type 2 diabetes DPP-4 inhibition + metformin Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden Abstract: Inhibition of dipeptidyl peptidase-4 (DPP-4) as a novel therapy for type 2 diabetes is based on prevention of the inactivation process of bioactive peptides, the most important in the context of treatment of diabetes of which is glucagon-like peptide-1 (GLP-1). Most clinical experience with DPP-4 inhibition is based on vildagliptin (GalvusR, Novartis) and sitagliptin (JanuviaR, Merck). These compounds improve glycemic control both in monotherapy and in combination with other oral hyperglycemic agents. Both have also been shown to efficiently improve glycemic control when added to ongoing metformin therapy in patients with inadequate glycemic control. Under that condition, they reduce HbA1c levels by 0.65%1.1% (baseline HbA1c 7.28.7%) in studies up to 52 weeks of duration in combination versus continuous therapy with metformin alone. Sitagliptin has also been examined in initial combination therapy with metformin have; HbA1c was reduced by this combination by 2.1% (baseline HbA1c 8.8%) after 24 weeks of treatment. Both fasting and prandial glucose are reduced by DPP-4 inhibition in combination with metformin in association with improvement of insulin secretion and insulin resistance and increase in concentrations of active GLP-1. The combination of DPP-4 inhibition and metformin has been shown to be highly tolerable with very low risk of hypoglycemia. Hence, DPP-4 inhibition in combination with metformin is an efficient, safe and tolerable combination therapy for type 2 diabetes. Keywords: DPP-4 inhibition, sitagliptin, vildagliptin, metformin, type 2 diabetes This work is published and licensed by Dov Continue reading >>

Two New Dpp-4 Inhibitor/metformin Combination Therapies Approved In The Us

Two New Dpp-4 Inhibitor/metformin Combination Therapies Approved In The Us

Two New DPP-4 Inhibitor/Metformin Combination Therapies Approved in the US In late January, the FDA granted approval to two new combination therapies for the treatment of type 2 diabetes Mercks Janumet XR and Eli Lilly/Boehringer Ingelheims Jentadueto. Both therapies combine a DPP-4 inhibitor and metformin (both already approved therapies for type 2 diabetes) into a single pill, increasing convenience over taking each drug separately. As background, DPP-4 inhibitors help prevent the destruction of the gut hormone GLP-1 in the body, which improves glucose control with minimal risk for hypoglycemia or weight gain. Meanwhile, metformin lowers blood glucose levels by decreasing glucose production by the liver. With the recent approval of Janumet XR and Jentadueto, there are now four different DPP-4 inhibitor and metformin combination therapies available in the US. Jentadueto is a combination of the DPP-4 inhibitor Tradjenta and metformin and is taken twice daily. Janumet (approved in 2007), and Janumet XR both contain the DPP-4 inhibitor Januvia, but differ in the formulation of metformin that is used. For this reason, Janumet is taken twice daily, whereas Janumet XR can be taken once a day. The only other currently approved once-daily DPP-4 inhibitor/metformin combination therapy in the US is Bristol-Myer Squibb/AstraZenecas Kombiglyze XR (saxagliptin plus metformin XR).We note that none of these combination therapies should be used in people with impaired kidney function because of increased risks for certain side effects (such as lactic acidosis). The manufacturers of both Janumet XR and Jentadueto have indicated that the drugs will be available at pharmacies shortly. LR/BK Continue reading >>

Efficacy Of Dpp-4 Inhibitors And Metformin As Initial Combo Therapy In Type 2 Diabetes

Efficacy Of Dpp-4 Inhibitors And Metformin As Initial Combo Therapy In Type 2 Diabetes

Home / Resources / Articles / Efficacy of DPP-4 Inhibitors and Metformin as Initial Combo Therapy in Type 2 Diabetes Efficacy of DPP-4 Inhibitors and Metformin as Initial Combo Therapy in Type 2 Diabetes DPP-4 may be a credible alternative for patients unable to tolerate metformin. The goal for this meta-analysis study was to provide an update on the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes. The researchers looked at these medications as first line treatments because of their popularity among diabetics for adjunct therapy on top of other medication regimens. The study was performed by utilizing a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials of DPP-4 inhibitors and metformin as initial combination therapy or as metformin monotherapy in patients with type 2 diabetes. The majority of the data was taken in December 2012 and included medications such as: alogliptin, dutogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin, and metformin. All randomized controlled trials were selected for meta-analysis if they specifically compared DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy. The second inclusion parameter used in the study took into consideration the duration of treatment. All trials incorporated into the study had to be greater than 12 weeks to be included. A final reporting criteria for the medication study was the reported data on HbA1c change, fasting plasma glucose change, weight change, adverse cardiovascular events, hypoglycemia, or gastrointestinal adverse events. Results from the review study came from 8 randomized Continue reading >>

Efficacy And Safety Of Dipeptidyl Peptidase-4 Inhibitors In Combination With Metformin

Efficacy And Safety Of Dipeptidyl Peptidase-4 Inhibitors In Combination With Metformin

, Volume 30, Issue4 , pp 337353 | Cite as Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Combination with Metformin Use of dipeptidyl peptidase-4 (DPP-4) inhibitors is prevalent for the treatment of type 2 diabetes since they have fewer adverse effects compared with other non-insulin medications currently available; however, as monotherapy, the glycosylated hemoglobin (HbA1c)-lowering power of these agents is moderate. The aim of this article is to evaluate the current literature regarding the safety and efficacy of DPP-4 inhibitors in combination with metformin. A literature search was conducted through MEDLINE (from 1950 to October 2012), PubMed (from 1966 to October 2012), EMBASE (from 1966 to October 2012), and International Pharmaceutical Abstracts (from 1970 to October 2012) using the search terms sitagliptin, linagliptin, alogliptin, vildagliptin, saxagliptin, and metformin. Studies that did not evaluate the DPP-4 inhibitors in combination with metformin and those that were not phase 3, were excluded. Many of the studies evaluated DPP-4 inhibitors in combination with metformin versus glucagon-like peptide-1 (GLP-1) agonists, placebo, DPP-4 inhibitors as monotherapy, thiazolidinediones, and sulfonylureas. The results of these noninferiority trials were that DPP-4 inhibitors as a whole are noninferior to either each other or other agents except for GLP-1 agonists. Also, in superiority studies, GLP-1 agonists proved to have greater HbA1c lowering. In summary, DPP-4 inhibitors play a vital role in the treatment of diabetes. They have relatively limited adverse effects, especially regarding hypoglycemia. DPP-4 inhibitors in combination with metformin are generally well tolerated and are available as combination products to reduce pill burden and enhance Continue reading >>

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