DOCSLIB.ORG

Dapagliflozin Plus Saxagliptin Add-On Therapy Compared with Insulin In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dapagliflozin Plus Saxagliptin Add-On Therapy Compared with Insulin In EMERGING THERAPIES: DRUGS AND REGIMENS Diabetes Care 1 fl Tina Vilsbøll,1 Ella Ekholm,2 Eva Johnsson,2 Dapagli ozin Plus Saxagliptin Nalina Dronamraju,3 Serge Jabbour,4 and Add-on Therapy Compared With Marcus Lind5 Insulin in Patients With Type 2 Diabetes Poorly Controlled by Metformin With or Without Sulfonylurea Therapy: A Randomized Clinical Trial https://doi.org/10.2337/dc18-1988 OBJECTIVE This study evaluated whether an oral combination of a sodium–glucose cotrans- porter 2 inhibitor and a dipeptidyl peptidase 4 inhibitor achieved glycemic control similar to basal insulin in patients with type 2 diabetes, poorly controlled with metformin, without increasing hypoglycemia or body weight. RESEARCH DESIGN AND METHODS In a multinational, open-label, randomized, phase 3 trial (NCT02551874), adults with type 2 diabetes inadequately controlled on metformin, with or without sulfonyl- urea, were randomized (1:1) to receive dapagliflozin (DAPA) plus saxagliptin (SAXA) or titrated insulin glargine (INS). The primary end point was change in glycated hemoglobin A1c (HbA1c) from baseline to week 24. DAPA + SAXA treatment was tested for noninferiority versus INS. 1Steno Diabetes Center Copenhagen, University of Copenhagen, Copenhagen, Denmark 2 RESULTS AstraZeneca Gothenburg, Molndal,¨ Sweden 3 fi 6 6 6 AstraZeneca, Gaithersburg, MD The ef cacy data set included 643 patients (mean SD HbA1c, 9.1 1.0% [75 4Division of Endocrinology, Thomas Jefferson 11 mmol/mol]). At week 24, DAPA + SAXA treatment versus INS resulted in University Hospital, Philadelphia, PA 5Institute of Medicine, University of Gothenburg, noninferior reductions in HbA1c (adjusted mean 6 SE change, 21.7 6 0.1% vs. 21.5 6 0.1% [18.3 6 0.7 mmol/mol vs. 16.8 6 0.7 mmol/mol]; P = 0.118), Gothenburg, Sweden significantly different body weight change (between-group difference, 23.64 kg Corresponding author: Tina Vilsbøll, t.vilsboll @dadlnet.dk [95% CI 24.20 to 23.09]; P < 0.001), fewer patients with confirmed hypoglycemia P < < Received 20 September 2018 and accepted 10 (21.3% vs. 38.4%, 0.001), more patients achieving HbA1c 7.0% (53 mmol/mol) May 2019 P without hypoglycemia (20.9% vs. 13.1%, = 0.008), and a similar proportion of Clinical trial reg. no. NCT02551874, clinicaltrials patients achieving HbA1c <7.0% (33.2% vs. 33.5%, P = 0.924). Mean reductions in .gov 24-h glucose measurements from baseline to week 2 were greater with DAPA + This article contains Supplementary Data online SAXA than with INS (P < 0.0001). No patients in the DAPA + SAXA group and three at http://care.diabetesjournals.org/lookup/suppl/ patients (0.9%) in the INS group experienced severe hypoglycemia. doi:10.2337/dc18-1988/-/DC1. © 2019 by the American Diabetes Association. CONCLUSIONS Readers may use this article as long as the work Adding DAPA + SAXA to insulin-na¨ıve patients with poorly controlled type 2 dia- is properly cited, the use is educational and not for profit, and the work is not altered. More infor- betes achieved similar glycemic control, a lower risk of hypoglycemia, and a clin- mation is available at http://www.diabetesjournals ically relevant body weight difference compared with basal INS. .org/content/license. Diabetes Care Publish Ahead of Print, published online June 4, 2019 2 Dual Add-on Oral Therapy Versus Insulin Diabetes Care Most patients with type 2 diabetes are body weight gain, which may reduce or Independent Ethics Committee before treated with metformin as a first-line patient compliance (13). Furthermore, initiation of the study. glucose-lowering monotherapy, as rec- insulin is administered by injection, ommended by treatment guidelines and titration is mandatory to obtain Participants and Eligibility Criteria (1,2). However, patients receiving met- acceptable glycemic control. Many pa- Adults ($18 years) with type 2 diabetes formin monotherapy often require the tients are reluctant to use insulin owing and inadequate glycemic control (HbA1c subsequent addition of one or more to psychological barriers, and health care 8.0–12.0% [64–108 mmol/mol]), who further glucose-lowering agents to achieve providers must have specialist knowl- had been receiving a stable dose of and maintain glycemic control as the dis- edge and resources to initiate and guide metformin ($1,500 mg/day), with or ease progresses (2). Sulfonylureas are the patients in the use of insulin therapy. It is without a stable dose of sulfonylurea most commonly prescribed drug after likely that many clinicians perceive in- ($50% maximum dose) for at least metformin, although treatment with this sulin to be more efficacious than oral 8 weeks before screening, were eligible drug class is associated with an increased therapies in patients with high HbA1c for enrollment. Participants were re- risk of hypoglycemia and weight gain (2). levels, because studies comparing insulin quired to have a maximum BMI of 2 An ideal therapy should be efficacious, with oral agents have generally excluded 45.0 kg/m at screening and a maximum achieve glycated hemoglobin A1c (HbA1c) these patients. No studies to date have fasting plasma glucose (FPG) measure- targets without hypoglycemia through evaluated whether an oral combination ment of 270 mg/dL at baseline. All par- complementary mechanisms of actions, of two modern glucose-lowering agents ticipants provided written, informed and result in weight reduction. Sodium– may achieve a similar glucose reduction consent. glucose cotransporter 2 (SGLT-2) inhib- as initiation and titration of a once-daily Key exclusion criteria were type 1 di- itors, glucagon-like peptide 1 receptor basal insulin analog in patients with abetes, cardiovascular disease (including agonists (GLP-1RAs), and dipeptidyl pep- type 2 diabetes inadequately controlled myocardial infarction; cardiac surgery or tidase 4 inhibitors (DPP-4is) are glucose- with metformin. revascularizations; valvular disease or lowering drugs that are recommended by Here, we report the results from a repair; unstable angina; unstable conges- international guidelines for use in com- randomized, open-label, 24-week, phase tive heart failure; transient ischemic attack bination with metformin (3). SGLT-2 in- 3 trial evaluating the efficacy and safety or significant cerebrovascular disease; hibitors promote urinary excretion of of DAPA plus SAXA add-on therapy versus unstable or previously undiagnosed ar- excess glucose by inhibiting renal glucose titrated insulin in patients with type 2 rhythmia; congestive heart failure de- reabsorption and act independently of diabetes inadequately controlled by met- fined as New York Heart Association insulin (4), whereas DPP-4is and GLP- formin with or without sulfonylurea ther- Functional Classification III and IV; un- 1RAs enhance glucose-dependent insulin apy. The primary objective of this study stable or acute congestive heart failure; secretion and suppress glucagon secre- was to determine whether DAPA plus and/or known left ventricular ejection tion (5). GLP-1RAs are generally recom- SAXA treatment was noninferior to ti- fraction of #40%) within 3 months of fi mended by clinical guidelines as the first trated insulin in reducing HbA1c. Secondary screening, severe hepatic insuf ciency, injectable medication for patients with objectives included effects on hypogly- and a medical history of diabetic keto- type 2 diabetes (6). cemia and body weight. acidosis or renal impairment (defined as The SGLT-2 inhibitor dapagliflozin creatinine clearance ,60 mL/min or se- (DAPA) and the DPP-4i saxagliptin (SAXA) RESEARCH DESIGN AND METHODS rum creatinine $1.5 mg/dL in men improve glycemic control in patients with Study Design or $1.4 mg/dL in women). type 2 diabetes when used as mono- This international, multicenter, randomized, therapies (7–9) or in combination with open-label, active-controlled, parallel-group, Randomization metformin (10,11). Moreover, dual ad- 24-week phase 3b trial (clinicaltrials.gov Participants were randomized 1:1 using dition of DAPA plus SAXA to metformin identifier: NCT02551874) was conducted an interactive voice response system to resulted in greater reductions in HbA1c at 112 centers in 11 countries (Czech receive DAPA plus SAXA or titrated in- than either agent added to metformin Republic, Denmark, Germany, Hungary, sulin glargine (INS), stratified by use of alone (12). DAPA plus SAXA add-on to Mexico, Poland, Romania, South Africa, sulfonylurea with background metformin metformin is also associated with body Spain, Sweden, and U.S.). It consisted of a treatment, for 24 weeks (Supplementary weight reduction and a low risk of hy- 2-week lead-in period, during which par- Fig. 1). Randomization schedules were poglycemia and produces a similar safety ticipants received instruction on diet, exer- generated and kept by Bristol-Myers profile to that reported in previous stud- cise, and self-monitoring of glucose levels, Squibb. ies of these agents as monotherapy (7–9) followed by a 24-week treatment period. or as add-on therapy (10–12). The study was conducted in accor- Interventions Insulin is an effective glucose-lowering dance with the ethical principles outlined DAPA, 10 mg/day (Bristol-Myers Squibb, agent for patients with type 2 diabetes in the Declaration of Helsinki and Good New Brunswick, NJ), and SAXA, 5 mg/day and is recommended as one of several Clinical Practice guidelines of the Inter- (Bristol-Myers Squibb, Mount Vernon, options for second- or third-line glucose- national Conference on Harmonization. IN), were administered orally in tablet lowering therapy by many clinical guide- The
Load more

Recommended publications
  • Treatment of Diabetes Mellitus
    TREATMENT OF DIABETES MELLITUS DIABETES is a condition that affects how the body makes energy from food. Food is broken down into sugar (glucose) in the body and released into the blood. When the blood sugar level rises after a meal, insulin responds to let the sugar into the cells to be used as energy. In diabetes, the body either does not make enough insulin or it stops responding to insulin as well as it should. This results in sugar staying in the blood and leads to serious health problems over time. DIAGNOSIS OF DIABETES1 • A1C Test: Lab test measuring average blood sugar over past two to three months • Fasting Blood Sugar Test: Lab test measuring blood sugar after eight hours of no food or drink • Oral Glucose Tolerance Test (OGTT): Measures blood sugar before and two hours after drinking a specific sugary liquid • Random Blood Sugar Test: Measures blood sugar at a moment in time, without any kind of preparation (like fasting) FASTING BLOOD ORAL GLUCOSE TOLERANCE RANDOM BLOOD RESULT A1C TEST SUGAR TEST TEST SUGAR TEST Diabetes ≥ 6.5% ≥126 mg/dL ≥ 200 mg/dL ≥ 200 mg/dL Prediabetes 5.7 – 6.4% 100 – 125 mg/dL 140 – 199 mg/dL N/A Normal < 5.7% ≤99 mg/dL < 140 mg/dL N/A NON-DRUG TREATMENTS2 THERAPY COST WHAT TO EXPECT Diet (Mediterranean diet) and exercise (30 minutes a day, five days a week of moderate- Weight loss $-$$ intensity exercise); 7% weight loss decreases risk of diabetes3 Psychological intervention $$-$$$ Psychotherapy may reduce diabetic distress and improve glycemic control4,5 nationalcooperativerx.com PRESCRIPTION TREATMENTS
    [Show full text]
  • Dapagliflozin – Structure, Synthesis, and New Indications
    Pharmacia 68(3): 591–596 DOI 10.3897/pharmacia.68.e70626 Review Article Dapagliflozin – structure, synthesis, and new indications Stefan Balkanski1 1 Bulgarian Pharmaceutical Union, Sofia, Bulgaria Corresponding author: Stefan Balkanski ([email protected]) Received 24 June 2021 ♦ Accepted 4 July 2021 ♦ Published 4 August 2021 Citation: Balkanski S (2021) Dapagliflozin – structure, synthesis, and new indications. Pharmacia 68(3): 591–596.https://doi. org/10.3897/pharmacia.68.e70626 Abstract Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitors used in the treatment of patients with type 2 diabetes. An aryl glycoside with significant effect as glucose-lowering agents, Dapagliflozin also has indication for patients with Heart Failure and Chronic Kidney Disease. This review examines the structure, synthesis, analysis, structure activity relationship and uses of the prod- uct. The studies behind this drug have opened the doors for the new line of treatment – a drug that reduces blood glucoses, decreases the rate of heart failures, and has a positive effect on patients with chronic kidney disease. Keywords Dapagliflozin, SGLT2-inhibitor, diabetes, heart failure Structure of dapagliflozin against diabetes (Lee et al. 2005; Lemaire 2012; Mironova et al. 2017). Embodiments of (SGLT-2) inhibitors include C-glycosides have a remarkable rank in medicinal chemis- dapagliflozin, canagliflozin, empagliflozin and ipragliflozin, try as they are considered as universal natural products shown in Figure 1. It has molecular formula of C24H35ClO9. (Qinpei and Simon 2004). Selective sodium-dependent IUPAC name (2S,3R,4R,5S,6R)-2-[4-chloro-3-[(4- glucose cotransporter 2 (SGLT-2) inhibitors are potent ethoxyphenyl)methyl]phenyl]-6-(hydroxymethyl)oxa- medicinal candidates of aryl glycosides that are functional ne-3,4,5-triol;(2S)-propane-1,2-diol;hydrate.
    [Show full text]
  • Onglyza (Saxagliptin) Uses, Dosage, Side Effects - Drugs.Com 04/07/2015 Insulin Pump – Tubeless Feel the Freedom for Yourself! Learn About the Omnipod®
    Onglyza (saxagliptin) Uses, Dosage, Side Effects - Drugs.com 04/07/2015 Insulin Pump – Tubeless Feel The Freedom For Yourself! Learn About The OmniPod®. Browse all medications A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Advanced Search Phonetic Search Drugs A-Z Pill Identifier Interactions Checker News Health Professionals Q & A Mednotes Apps Home → Conditions → Diabetes, Type 2 → Onglyza Print Share Sign In or Register Onglyza Related Information Availability Pregnancy Category Generic Name: saxagliptin (SAX a GLIP tin) Prescription only No proven risk in Brand Names: Onglyza humans CSA Schedule Not a controlled drug Approval History Drug history at FDA Overview Side Effects Dosage Interactions For Professionals More Reviews Average User Rating Insulin Pump – Tubeless Feel The Freedom For Yourself! Learn About The 9 User Reviews 7.6 Rate it! OmniPod® Drug Class What is Onglyza? Dipeptidyl peptidase 4 inhibitors Onglyza (saxagliptin) is an oral diabetes medicine that helps control blood sugar levels . It works by regulating Related Drugs the levels of insulin your body produces after Diabetes, Type 2 eating. metformin Onglyza is for people with type 2 diabetes. It is insulin aspart Januvia sometimes used in combination with other glipizide diabetes medications, but is not for treating glimepiride type 1 diabetes . Lantus Onglyza may also be used for purposes not Invokana listed in this medication guide. Victoza glyburide Levemir Humalog Actos Important information Janumet You should not use Onglyza if you are in a state of diabetic ketoacidosis (call your doctor for Glucophage treatment with insulin).
    [Show full text]
  • Komboglyze, INN-Saxagliptin, Metformin
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Komboglyze 2.5 mg/850 mg film-coated tablets Komboglyze 2.5 mg/1,000 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Komboglyze 2.5 mg/850 mg film-coated tablets Each tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 850 mg of metformin hydrochloride. Komboglyze 2.5 mg/1,000 mg film-coated tablets Each tablet contains 2.5 mg of saxagliptin (as hydrochloride) and 1,000 mg of metformin hydrochloride. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet (tablet). Komboglyze 2.5 mg/850 mg film-coated tablets Light brown to brown, biconvex, round, film-coated tablets, with “2.5/850” printed on one side and “4246” printed on the other side, in blue ink. Komboglyze 2.5 mg/1,000 mg film-coated tablets Pale yellow to light yellow, biconvex, oval shaped, film-coated tablets, with “2.5/1000” printed on one side and “4247” printed on the other side, in blue ink. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Komboglyze is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control: in patients inadequately controlled on their maximally tolerated dose of metformin alone in combination with other medicinal products for the treatment of diabetes, including insulin, in patients inadequately controlled with metformin and these medicinal products (see sections 4.4, 4.5 and 5.1 for available data on different combinations) in patients already being treated with the combination of saxagliptin and metformin as separate tablets.
    [Show full text]
  • Qtern (Dapagliflozin/Saxagliptin) – New Drug Approval
    Qtern® (dapagliflozin/saxagliptin) – New drug approval • On February 28, 2017, AstraZeneca announced the FDA approval of Qtern (dapagliflozin/saxagliptin) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with Farxiga® (dapagliflozin) or who are already treated with dapagliflozin and Onglyza® (saxagliptin). • Qtern is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis, and it should only be used in patients who tolerate 10 mg of dapagliflozin. • Qtern combines two anti-hyperglycemic agents, dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, and saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor. • The efficacy of Qtern was evaluated in a study of 315 T2DM patients. Patients were randomized to saxagliptin or placebo, in combination with dapagliflozin and metformin. — Patients treated with add-on saxagliptin therapy had significantly greater reductions in HbA1c from baseline vs. the placebo group (-0.5% vs. -0.2%, respectively; difference between groups in HbA1c: -0.4%, p < 0.0001). — The proportion of patients achieving HbA1c < 7% at week 24 was 35.3% in the saxagliptin group vs. 23.1% in the placebo group. • Qtern is contraindicated in patients with a history of a serious hypersensitivity reaction to dapagliflozin or to saxagliptin (eg, anaphylaxis, angioedema or exfoliative skin conditions), and in patients with moderate to severe renal impairment (eGFR < 45 mL/min/1.73 m2), end-stage renal disease, or on dialysis. • Warnings and precautions of Qtern include pancreatitis, heart failure, hypotension, ketoacidosis, acute kidney injury and impairment in renal function, urosepsis and pyelonephritis, hypoglycemia with concomitant use of insulin or insulin secretagogues, genital mycotic infections, increases in low- density lipoprotein cholesterol, bladder cancer, severe and disabling arthralgia, and bullous pemphigoid.
    [Show full text]
  • Reference ID: 3912436 FULL PRESCRIBING INFORMATION
    HIGHLIGHTS OF PRESCRIBING INFORMATION Hypoglycemia: In add-on to sulfonylurea, add-on to insulin, and add-on These highlights do not include all the information needed to use to metformin plus sulfonylurea trials, confirmed hypoglycemia was ONGLYZA safely and effectively. See full prescribing information for more common in patients treated with ONGLYZA compared to placebo. ONGLYZA. When used with an insulin secretagogue (e.g., sulfonylurea) or insulin, a lower dose of insulin secretagogue or insulin may be required to ONGLYZA (saxagliptin) tablets, for oral use minimize the risk of hypoglycemia. (5.3, 6.1) Initial U.S. Approval: 2009 Hypersensitivity-Related Events (e.g., urticaria, facial edema): More common in patients treated with ONGLYZA than in patients treated -------------------------- RECENT MAJOR CHANGES -------------------------- with placebo; and postmarketing reports of serious hypersensitivity Warnings and Precautions reactions such as anaphylaxis, angioedema, and exfoliative skin Pancreatitis (5.1) 4/2016 conditions. Promptly discontinue ONGLYZA, assess for other potential Heart Failure (5.2) 4/2016 causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes. (5.4, 6.1, 6.2) --------------------------- INDICATIONS AND USAGE -------------------------- Arthralgia: Severe and disabling arthralgia has been reported in patients ONGLYZA is a dipeptidyl peptidase-4 (DPP4) inhibitor indicated as an taking DPP4 inhibitors. Consider as a possible cause for severe joint adjunct to diet and exercise to improve glycemic control in adults with type 2 pain and discontinue drug if appropriate. (5.5) diabetes mellitus. (1.1, 14) Macrovascular Outcomes: There have been no clinical studies Limitation of use: establishing conclusive evidence of macrovascular risk reduction with Not used for the treatment of type 1 diabetes mellitus or diabetic ONGLYZA or any other antidiabetic drug.
    [Show full text]
  • 202293Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 202293Orig1s000 RISK ASSESSMENT and RISK MITIGATION REVIEW(S) Department of Health and Human Services Public Health Service Food and Drug Administration Center for Drug Evaluation and Research Office of Surveillance and Epidemiology Office of Medication Error Prevention and Risk Management Final Risk Evaluation and Mitigation Strategy (REMS) Review Date: December 20, 2013 Reviewer(s): Amarilys Vega, M.D., M.P.H, Medical Officer Division of Risk Management (DRISK) Team Leader: Cynthia LaCivita, Pharm.D., Team Leader DRISK Drug Name(s): Dapagliflozin Therapeutic Class: Antihyperglycemic, SGLT2 Inhibitor Dosage and Route: 5 mg or 10 mg, oral tablet Application Type/Number: NDA 202293 Submission Number: Original, July 11, 2013; Sequence Number 0095 Applicant/sponsor: Bristol-Myers Squibb and AstraZeneca OSE RCM #: 2013-1639 and 2013-1637 *** This document contains proprietary and confidential information that should not be released to the public. *** Reference ID: 3426343 1 INTRODUCTION This review documents DRISK’s evaluation of the need for a risk evaluation and mitigation strategy (REMS) for dapagliflozin (NDA 202293). The proposed proprietary name is Forxiga. Bristol-Myers Squibb and AstraZeneca (BMS/AZ) are seeking approval for dapagliflozin as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Bristol-Myers Squibb and AstraZeneca did not submit a REMS or risk management plan (RMP) with this application. At the time this review was completed, FDA’s review of this application was still ongoing. 1.1 BACKGROUND Dapagliflozin. Dapagliflozin is a potent, selective, and reversible inhibitor of the human renal sodium glucose cotransporter 2 (SGLT2), the major transporter responsible for renal glucose reabsorption.
    [Show full text]
  • Real-Life Prescribing of SGLT2 Inhibitors: How to Handle the Other Medications, Including
    Kidney360 Publish Ahead of Print, published on February 1, 2021 as doi:10.34067/KID.0000412021 Real-life prescribing of SGLT2 inhibitors: How to handle the other medications, including glucose-lowering drugs and diuretics David Lam1 and Aisha Shaikh1,2 1Icahn School of Medicine at Mount Sinai, Dept. of Medicine, New York, NY 2James J. Peters VA Medical Center, Dept. of Medicine, Bronx, NY Corresponding Author: Aisha Shaikh, MD James J. Peters VA Medical Center 130 w. Kingsbridge Road Bronx, NY – 10468 Email: [email protected] Phone: 718-584-9000, Ext# 6630 Copyright 2021 by American Society of Nephrology. Introduction Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have emerged as an effective therapy for improving outcomes in diabetic and non-diabetic kidney disease (1, 2). Clinical trials have demonstrated the benefits of SGLT2is for secondary prevention of adverse cardiovascular (CV) effects in patients with established atherosclerotic disease and/or heart failure with reduced ejection fraction (3-7). It is imperative for clinicians to assess the use of SGLT2is in medically eligible patients and prescribe these agents when appropriate. Despite the overwhelming evidence of the benefits of SGLT2i therapy, the prescription rate remains dismally low particularly among patients most likely to benefit from cardiorenal protective effects (8). Several potential factors contribute to low SGLT2i prescription rate including prescriber hesitancy, treatment inertia and high drug cost. In this article, we review clinical indications for SGLT2i use, therapeutic and adverse effects, and our approach to handling concomitant medications. Clinical indications for SGLT2i Use 1. Type 2 diabetes mellitus (T2DM) and albuminuric kidney disease (albuminuria of ≥ 200 mg/gram of creatinine plus eGFR of 25 – 90 ml/min/1.73 m2).
    [Show full text]
  • SGLT2) Inhibitors (Gliflozins) in Adults with Type 2 Diabetes (T2DM
    Sodium-glucose cotransporter-2 (SGLT2) inhibitors (Gliflozins) in Adults with Type 2 Diabetes (T2DM) There are currently four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ertugliflozin) licensed in the UK for the management of adults with T2DM. No head to head trials between the SGLT2 inhibitors have been conducted. As at December 2019, clinical outcome data is available for three of the four SGLT2 inhibitors around their cardiovascular effects in people with T2DM. Ertugliflozin is still to report on this data. This document summarises the key prescribing considerations. NICE Technology Appraisal Recommendation NICE makes recommendations for when SGLT2 inhibitors can be considered in adults with T2DM; Hertfordshire Medicines Management Committee Recommendations are in line with NICE guidance: Monotherapy NICE TA 390: Canagliflozin, Dapagliflozin and Empagliflozin and NICE TA 572: Ertugliflozin as monotherapies for treating T2DM Monotherapy recommended as option in adults for whom metformin is contraindicated or not tolerated and when diet & exercise alone do not provide adequate glycaemic control, only if: •a DPP‑4 inhibitor would otherwise be prescribed and •a sulfonylurea or pioglitazone is not appropriate. Dual therapy NICE TA 315: Canagliflozin, NICE TA288: Dapagliflozin, TA 336: Empagliflozin, TA 572: Ertugliflozin as combination therapies for treating T2DM In a dual therapy regimen in combination with metformin is recommended as an option, only if: •a sulfonylurea is contraindicated or not tolerated or •the person is at significant risk of hypoglycaemia or its consequences. In combination with insulin NICE TA 315: Canagliflozin, NICE TA288: Dapagliflozin, TA 336: Empagliflozin in combination with insulin with or without other antidiabetic drugs is recommended as an option.
    [Show full text]
  • KOMBIGLYZE XR Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------WARNINGS AND PRECAUTIONS----------------------- These highlights do not include all the information needed to use Lactic acidosis: Warn patients against excessive alcohol intake. KOMBIGLYZE XR safely and effectively. See full prescribing KOMBIGLYZE XR not recommended in hepatic impairment and information for KOMBIGLYZE XR. contraindicated in renal impairment. Ensure normal renal function KOMBIGLYZE XR (saxagliptin and metformin HCl extended-release) before initiating and at least annually thereafter. Temporarily tablets discontinue KOMBIGLYZE XR in patients undergoing radiologic Initial U.S. Approval: 2010 studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and WARNING: LACTIC ACIDOSIS fluids. (4, 5.1, 5.3, 5.4, 5.7, 5.10, 5.11) See full prescribing information for complete boxed warning. There have been postmarketing reports of acute pancreatitis in patients Lactic acidosis can occur due to metformin accumulation. The taking saxagliptin. If pancreatitis is suspected, promptly discontinue risk increases with conditions such as sepsis, dehydration, excess KOMBIGLYZE XR. (5.2) alcohol intake, hepatic impairment, renal impairment, and acute Vitamin B12 deficiency: Metformin may lower vitamin B12 levels. congestive heart failure. (5.1) Measure hematological parameters annually. (5.5, 6.1) Symptoms include malaise, myalgias, respiratory distress, Hypoglycemia: When used with an insulin
    [Show full text]
  • Saxagliptin / Metformin Hcl Extended-Release) Tablets
    For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only (Saxagliptin / Metformin HCl extended-release) tablets. KOMBIGLYZETM XR Abbreviated Prescribing Information INDICATIONS AND USAGE: KombiglyzeTM XR is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate. IMPORTANT LIMITATIONS OF USE: KombiglyzeTM XR should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis; it has not been studied in patients with a history of pancreatitis. DOSAGE AND ADMINISTRATION: Generally should be administered once daily with the evening meal, with gradual dose titration to reduce the gastrointestinal side effects associated with metformin. • The recommended starting dose in patients who need 5 mg of saxagliptin and who are not currently treated with metformin is 5 mg saxagliptin/500 mg metformin extended-release. In patients treated with metformin, the dose should provide metformin at the dose already being taken, or the nearest therapeutically appropriate dose. • Patients who need 2.5 mg saxagliptin in combination with metformin extended-release may be treated with KombiglyzeTM XR 2.5 mg/1000 mg. • The maximum daily recommended dose is 5 mg for saxagliptin and 2000 mg for metformin extended-release. When co-administered with strong CYP3A4/5 inhibitors, limit the dose to 2.5 mg/1000 mg once daily. • When KOMBIGLYZETM XR is used in combination with an insulin secretagogue (e.g. sulphonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to minimise the risk of hypoglycaemia.
    [Show full text]
  • Linagliptin (Tradjenta) for the Treatment of Diabetes Mellitus KAREN WHALEN, Pharmd, BCPS, CDE, and KAREN R
    STEPS New Drug Reviews Linagliptin (Tradjenta) for the Treatment of Diabetes Mellitus KAREN WHALEN, PharmD, BCPS, CDE, and KAREN R. SANDO, PharmD, CDE University of Florida College of Pharmacy, Gainesville, Florida STEPS new drug reviews Linagliptin (Tradjenta) is a dipeptidyl-peptidase-4 (DPP-4) inhibitor labeled for the treat- cover Safety, Tolerability, ment of type 2 diabetes mellitus. Similar to sitagliptin (Januvia) and saxagliptin (Onglyza), Effectiveness, Price, and Simplicity. Each indepen- linagliptin delays the breakdown of endogenous incretin hormones such as glucagon-like dent review is provided peptide 1 and glucose-dependent insulinotropic polypeptide. These hormones, when secreted by authors who have no in response to food intake, stimulate postmeal insulin secretion, inhibit glucagon release, financial association with improve satiety, and slow gastric emptying.1,2 Linagliptin can be used alone or in combination the drug manufacturer. with metformin (Glucophage), sulfonylureas, pioglitazone (Actos), or insulin. The series coordinator for AFP is Allen F. Shaugh- nessy, PharmD, Tufts Drug Dosage Dose form Cost* University Family Medicine Residency Program at Linagliptin (Tradjenta) 5 mg daily 5-mg tablet $254 for 30 tablets Cambridge Health Alli- ance, Malden, Mass. *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com A collection of STEPS pub- (accessed October 1, 2012). lished in AFP is available at http://www.aafp.org/ afp/steps. SAFETY control should be used in patients receiving Few severe adverse effects have been associ- strong inducers of cytochrome P450 3A4 ated with linagliptin. When used alone or or P-glycoprotein, such as rifampin. Lina- with metformin or pioglitazone, linagliptin gliptin is a U.S.
    [Show full text]