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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 -
Combining a Glucagon-Like Peptide-1 Receptor Agonist with Basal Insulin: the Why and How
Combining a Glucagon-like Peptide-1 Receptor Agonist with Basal Insulin: The Why and How Case Study Mary is a 61 year-old female diagnosed with type 2 diabetes mellitus (T2DM) 8 years ago. She was initially managed with the combination of lifestyle modification and metformin. Since that time she was treated with a sulfonylurea, but it was discontinued due to symptomatic hypoglycemia. She was also treated with pioglitazone, but significant fluid retention led to it discontinuation. A year-and-a- half ago, basal insulin was added to her lifestyle and metformin management. She now administers 52 units (0.62 units/kg) once daily at bedtime. Since starting basal insulin, she has experienced 3 episodes of mild hypoglycemia. Since her diagnosis, Mary’s HbA1c has never been <7.0%; her current HbA1c is 7.9%. Over the past month, her fasting plasma glucose (FPG) has ranged from 103 mg/dL to 136 mg/dL and her postprandial glucose (PPG) from 164 mg/dL to 213 mg/dL. She has gained 2.6 kg since starting basal insulin and her body mass index is now 31 kg/m2. Her blood pressure is 134/82 mmHg. She experiences occasional tingling in her feet. Eye examination reveals grade 1 retinopathy. Current medications are: metformin 1000mg twice daily, basal insulin 52 units once daily at bedtime, and hydrochlorothiazide 25 mg once daily. Her family physician notes that Mary’s FPG is reasonably well-controlled, yet her HbA1c and PPG remain elevated. He is also concerned about her episodes of hypoglycemia and weight gain and the evidence indicating microvascular damage. -
Januvia (Sitagliptin) Tablets
CENTER FOR DRUG EVALUATION AND RESEARCH Approval Package for: APPLICATION NUMBER: NDA 021995/S-013 Trade Name: JANUVIA Generic Name: Sitagliptin Sponsor: Merck & Co., Inc. Approval Date: 12/28/2009 Indications: JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: NDA 021995/S-013 CONTENTS Reviews / Information Included in this NDA Review. Approval Letter X Other Action Letters X Labeling X Summary Review Officer/Employee List Office Director Memo Cross Discipline Team Leader Review Medical Review(s) X Chemistry Review(s) Environmental Assessment Pharmacology Review(s) X Statistical Review(s) Microbiology Review(s) Clinical Pharmacology/Biopharmaceutics Review(s) Risk Assessment and Risk Mitigation Review(s) X Proprietary Name Review(s) Other Review(s) X Administrative/Correspondence Document(s) X CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: NDA 021995/S-013 APPROVAL LETTER DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 021995/S-013 SUPPLEMENT APPROVAL Merck & Co., Inc. Attention: Richard J. Swanson, Ph.D. Director, Regulatory Affairs P.O. Box 1000, UG2C-50 North Wales, PA 19454-1099 Dear Dr. Swanson: Please refer to your supplemental new drug application (S-013) dated and received March 5, 2009, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Januvia (sitagliptin) tablets. We also refer to your supplemental new drug application (b) (4) dated and received November 13, 2009. Your submission of November 13, 2009, also constitutes a complete response to our October 16, 2009, action letter for supplemental application S-013. -
Performance of the Insulin-Only Ilet Bionic Pancreas and The
e118 Diabetes Care Volume 44, June 2021 Performance of the Insulin-Only Luz E. Castellanos,1 Courtney A. Balliro,1 Jordan S. Sherwood,1 Rabab Jafri,1 iLet Bionic Pancreas and the Mallory A. Hillard,1 Evelyn Greaux,1 Rajendranath Selagamsetty,2 Hui Zheng,3 Bihormonal iLet Using Firas H. El-Khatib,2 Edward R. Damiano,2,4 and Dasiglucagon in Adults With Type Steven J. Russell1 1 Diabetes in a Home-Use Setting Diabetes Care 2021;44:e118–e120 | https://doi.org/10.2337/dc20-1086 Reductions in blood glucose levels in with insulin lispro (Eli Lilly) or aspart (Table 1). The mean CGM glucose and people with diabetes are often achieved (Novo Nordisk), the bihormonal iLet for time in range (70–180 mg/dL) were 149 at the expense of increased hypoglyce- 7dayswithdasiglucagon(4mg/mL) ±13mg/dLand72±8%,respectively,in mia. A novel approach is to automati- and insulin lispro or aspart, or both, us- the insulin-only period, and 139 ± 11 cally deliver microdose glucagon when ing the same glucose target (110 mg/ mg/dL and 79 ± 9%, respectively, in the automation of insulin delivery alone is dL), in random order. There were no re- bihormonal period. The mean daily car- not sufficient to prevent hypoglycemia. strictions on diet or exercise. The prima- bohydrates consumed to prevent or The approach requires a bihormonal de- ry outcomes were prespecified iLet treat hypoglycemia were 16 ± 13 g and vice and a stable form of glucagon or operational thresholds. The key second- 18 ± 21 g in the insulin-only and bihor- glucagon analog. -
TRULICITY, INN-Dulaglutide
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Trulicity 0.75 mg solution for injection in pre-filled pen Trulicity 1.5 mg solution for injection in pre-filled pen Trulicity 3 mg solution for injection in pre-filled pen Trulicity 4.5 mg solution for injection in pre-filled pen 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Trulicity 0.75 mg solution for injection in pre-filled pen Each pre-filled pen contains 0.75 mg of dulaglutide* in 0.5 ml solution. Trulicity 1.5 mg solution for injection in pre-filled pen Each pre-filled pen contains 1.5 mg of dulaglutide* in 0.5 ml solution. Trulicity 3 mg solution for injection in pre-filled pen Each pre-filled pen contains 3 mg of dulaglutide* in 0.5 ml solution. Trulicity 4.5 mg solution for injection in pre-filled pen Each pre-filled pen contains 4.5 mg of dulaglutide* in 0.5 ml solution. *produced in CHO cells by recombinant DNA technology. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection. Clear, colourless solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Type 2 Diabetes Mellitus Trulicity is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise • as monotherapy when metformin is considered inappropriate due to intolerance or contraindications • in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, see sections 4.4, 4.5 and 5.1. -
Pharmacokinetics of Omarigliptin, a Once-Weekly Dipeptidyl Peptidase-4 Inhibitor
Available online a t www.derpharmachemica.com ISSN 0975-413X Der Pharma Chemica, 2016, 8(12):292-295 CODEN (USA): PCHHAX (http://derpharmachemica.com/archive.html) Mini-review: Pharmacokinetics of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 Inhibitor Nermeen Ashoush a,b aClinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, British University in Egypt, El- Sherouk city, Cairo 11837, Egypt. bHead of Health Economics Unit, Center for Drug Research and Development (CDRD), Faculty of Pharmacy, British University in Egypt, El-Sherouk city, Cairo 11837, Egypt. _____________________________________________________________________________________________ ABSTRACT The dipeptidyl peptidase-4 (DPP-4) inhibitors are novel oral hypoglycemic drugs which have been in clinical use for the past 10 years. The drugs are safe, weight neutral and widely prescribed. There are currently many gliptins approved by FDA, namely sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin with several more in advanced stages of development. The gliptins may possess cardiovascular protective effects and their administration may promote β-cell survival; claims currently being evaluated in clinical and preclinical studies. The gliptins are an optional second-line therapy after metformin; they are generally well tolerated with low risk of hypoglycemia. The various compounds differ with respect to their pharmacokinetic properties; however, their clinical efficacy appears to be similar. The clinical differences between the various compounds -
TREATMENT of TYPE 2 DIABETES with BIPHASIC INSULIN ANALOGUES *Ali A
TREATMENT OF TYPE 2 DIABETES WITH BIPHASIC INSULIN ANALOGUES *Ali A. Rizvi Professor of Medicine, Department of Medicine and Director, Division of Endocrinology, University of South Carolina School of Medicine, Columbia, South Carolina, USA *Correspondence to [email protected] Disclosure: The author has received grant support, as principal investigator at the University of South Carolina site, from the National Institutes of Health (NIH) for the SPRINT Trial (Contract Number: HHSN268200900040C, ClinicalTrials.gov Identifier: NCT01206062). The contents of this paper do not necessarily represent the views of the NIH. Received: 29.03.16 Accepted: 09.09.16 Citation: EMJ Diabet. 2016;4[1]:74-83. ABSTRACT The majority of patients with Type 2 diabetes require insulin therapy for treating hyperglycaemia. There are several regimens available for insulin initiation and maintenance. Insulin analogues have been developed to mimic normal physiology as closely as possible. Biphasic analogues can target both fasting and postprandial hyperglycaemia, with the added advantage of being premixed and thus convenient for the patient. A practical and feasible option is to initiate insulin with one or more biphasic preparations at mealtimes, thus providing both basal and prandial coverage. Individual titration of dose and frequency of daily injections with biphasic insulin preparations has the potential for improving glycaemic control with a high degree of patient acceptance. Drawbacks include a more rigid regimen, a relative lack of flexibility, and a somewhat higher degree of glycaemic variability and hypoglycaemia when compared to multiple daily basal-bolus injections. Awareness of the advantages and limitations of biphasic insulin analogues can assist clinicians in their appropriate use for the treatment of patients with Type 2 diabetes. -
Sitagliptin: a New Class of Oral Drug for Type 2 Diabetes
JK SCIENCE DRUG REVIEW Sitagliptin: a New Class of Oral Drug for Type 2 Diabetes Dinesh K. Badyal, Jasleen Kaur Introduction Pharmacokinetics Type 2 diabetes is the most common form of the Bioavailability of sitagliptin is approximately 87%. Half- disease, accounting for about 90% to 95 % of all diagnosed life is between 8-14 hours. It is 38% bound to plasma cases of diabetes. In type 2 diabetes, the body does not proteins. It undergoes limited metabolism via CYP3A4 produce enough insulin or the cells ignore the insulin. and CYP2C8. Elimination is mainly through urine (5, 6). Over time, high blood sugar levels can increase the risk Clinical Use for serious complications, including heart disease, In October 2006, the U.S. Food and Drug blindness, nerve damage and kidney damage (1). Any Administration (FDA) approved sitagliptin as new oral hypoglycemic drug that can increase the control monotherapy and as add-on therapy to either of two other of blood glucose with fewer adverse effects in patients types of oral diabetes medications, metformin or with diabetes may be welcomed. Sitagliptin is the first thiazolidinediones to improve blood glucose control in and only prescription medication in a new class of oral patients with type 2 diabetes when diet and exercise are antihyperglycemic agents, which enhance the body's own not enough (5). In March, 2007 it was approved in ability to lower blood glucose when it is elevated (2). European Union. Sitagliptin is currently approved in 42 Mechanism of Action countries (7). The recommended dose of sitagliptin is Sitagliptin prolongs the activity of proteins that increase 100 mg once daily. -
Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly
2106 Diabetes Care Volume 38, November 2015 fi Wayne H.-H. Sheu,1 Ira Gantz,2 Safety and Ef cacy of Omarigliptin Menghui Chen,2 Shailaja Suryawanshi,2 Arpana Mirza,2 Barry J. Goldstein,2 (MK-3102), a Novel Once-Weekly Keith D. Kaufman,2 and Samuel S. Engel2 DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes Diabetes Care 2015;38:2106–2114 | DOI: 10.2337/dc15-0109 OBJECTIVE This study was conducted to determine the optimal dose of omarigliptin, a once- weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of patients with type 2 diabetes and evaluate the long-term safety of that dose. RESEARCH DESIGN AND METHODS In a multicenter, double-blind, 12-week, dose-range finding study, 685 oral antihy- perglycemic agent-na¨ıve or washed-out subjects with type 2 diabetes were random- ized to one of five once-weekly doses of omarigliptin (0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The primary efficacy end point was change from baseline in HbA1c, and secondary end points were 2-h postmeal glucose (PMG) and fasting plasma glucose (FPG). Analysis included all patients who received at least one dose of the study medication. Subjects who completed the base study were eligible to enter a 66-week extension study. RESULTS Once-weekly treatment for 12 weeks with omarigliptin provided dose-related reduc- 1Division of Endocrinology and Metabolism, De- partment of Internal Medicine, Taichung Veterans EMERGING TECHNOLOGIES AND THERAPEUTICS tions in HbA , 2-h PMG, and FPG. -
Type 2 Diabetes Adult Outpatient Insulin Guidelines
Diabetes Coalition of California TYPE 2 DIABETES ADULT OUTPATIENT INSULIN GUIDELINES GENERAL RECOMMENDATIONS Start insulin if A1C and glucose levels are above goal despite optimal use of other diabetes 6,7,8 medications. (Consider insulin as initial therapy if A1C very high, such as > 10.0%) 6,7,8 Start with BASAL INSULIN for most patients 1,6 Consider the following goals ADA A1C Goals: A1C < 7.0 for most patients A1C > 7.0 (consider 7.0-7.9) for higher risk patients 1. History of severe hypoglycemia 2. Multiple co-morbid conditions 3. Long standing diabetes 4. Limited life expectancy 5. Advanced complications or 6. Difficult to control despite use of insulin ADA Glucose Goals*: Fasting and premeal glucose < 130 Peak post-meal glucose (1-2 hours after meal) < 180 Difference between premeal and post-meal glucose < 50 *for higher risk patients individualize glucose goals in order to avoid hypoglycemia BASAL INSULIN Intermediate-acting: NPH Note: NPH insulin has elevated risk of hypoglycemia so use with extra caution6,8,15,17,25,32 Long-acting: Glargine (Lantus®) Detemir (Levemir®) 6,7,8 Basal insulin is best starting insulin choice for most patients (if fasting glucose above goal). 6,7 8 Start one of the intermediate-acting or long-acting insulins listed above. Start insulin at night. When starting basal insulin: Continue secretagogues. Continue metformin. 7,8,20,29 Note: if NPH causes nocturnal hypoglycemia, consider switching NPH to long-acting insulin. 17,25,32 STARTING DOSE: Start dose: 10 units6,7,8,11,12,13,14,16,19,20,21,22,25 Consider using a lower starting dose (such as 0.1 units/kg/day32) especially if 17,19 patient is thin or has a fasting glucose only minimally above goal. -
Januvia (Sitagliptin)
UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2021 P 3084-7 Program Step Therapy – Diabetes Medications- DPP4 Inhibitors Medication Januvia (sitagliptin)*, Janumet (sitagliptin/metformin immediate- release)*, Janumet XR (sitagliptin/metformin extended-release)* P&T Approval Date 10/2016, 10/2017, 1/2018, 10/2019, 4/2020, 5/2020, 5/2021 Effective Date 8/1/2021; Oxford only: 8/1/2021 1. Background: Januvia (sitagliptin)* is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Janumet (sitagliptin/metformin)* and Janumet XR (sitagliptin/metformin extended-release)* are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and metformin/metformin extended-release is appropriate. 2. Coverage Criteriaa: A. Januvia* will be approved based on the following criterion: 1. History of a three month trial resulting in a therapeutic failure, contraindication (e.g. risk factors for heart failure), or intolerance to both of the following (list reason for therapeutic failure, contraindication, or intolerance)b: a. Tradjenta (linagliptin) -AND- b. One of the following: (1) Nesina (alogliptin) (2) Onglyza (saxagliptin) Authorization will be issued for 12 months B. Janumet* and Janumet XR* will be approved based on the following criterion: 1. History of a three month trial resulting in a therapeutic failure, contraindication (e.g. risk factors for heart failure), or intolerance to all of the following (list reason for therapeutic failure, contraindication, or intolerance)b: a. Jentadueto (linagliptin/metformin immediate-release)/Jentadueto XR (linagliptin/metformin extended-release) -AND- b. -
Safety of Insulin Lispro and a Biosimilar Insulin Lispro When
DSTXXX10.1177/1932296817753644Journal of Diabetes Science and TechnologyThrasher et al 753644research-article2018 Original Article Journal of Diabetes Science and Technology 2018, Vol. 12(3) 680 –686 Safety of Insulin Lispro and a Biosimilar © 2018 Diabetes Technology Society Insulin Lispro When Administered Reprints and permissions: sagepub.com/journalsPermissions.nav Through an Insulin Pump DOI:https://doi.org/10.1177/1932296817753644 10.1177/1932296817753644 journals.sagepub.com/home/dst James Thrasher, MD1, Howard Surks, MD2, Irene Nowotny, PhD3, Suzanne Pierre, MSc4, Baerbel Rotthaeuser, PhD3, Karin Wernicke-Panten, MD3, and Satish Garg, MD5 Abstract Background: SAR342434 (U100; SAR-Lis; insulin lispro) is a biosimilar/follow-on to insulin lispro (U100; Ly-Lis). Similar pharmacokinetics/pharmacodynamics between the two products has been demonstrated in a hyperinsulinemic euglycemic clamp study. The current study evaluated the safety of SAR-Lis and Ly-Lis when administered by continuous subcutaneous insulin infusion (CSII; insulin pumps). Methods: This was a randomized, open-label, 2 × 4-week, two-arm crossover study in 27 patients with type 1 diabetes mellitus (NCT02603510). The main outcome was the incidence of infusion set occlusions (ISOs), defined as failure to correct hyperglycemia (plasma glucose ≥≥ 300 mg/dl) by 50 mg/dl within 60 minutes by insulin bolus via the pump. Secondary outcomes included intervals between infusion set changes, treatment-emergent adverse events (TEAEs) including infusion site, hypersensitivity reactions and hypoglycemic events, and safety. Results: The number of patients reporting at least one ISO was small: 6/25 patients on SAR-Lis reported 14 ISOs and 4/27 on Ly-Lis reported nine ISOs. The estimated difference in ISO risk for SAR-Lis versus Ly-Lis was 7.9% (95% CI, –1.90 to 17.73).