DOCSLIB.ORG

Growing Our Future in Diabetes Care: Where Are We Now and Where Are We Going?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Growing Our Future in Diabetes Care: Where Are We Now and Where Are We Going? GROWING OUR FUTURE IN DIABETES CARE: WHERE ARE WE NOW AND WHERE ARE WE GOING? Ashley Firm, Pharm.D. Lindsey Meston, Pharm.D. Disclosure Neither Dr. Firm nor Dr. Meston have anything to disclosure concerning possible financial or personal relationships with commercial entities (or their competitors) mentioned in this presentation. Objectives ■ Summarize key differences and updates to guidelines related to the care of diabetic patients, especially updates in the 2018 American Diabetes Association Standard of Medical Care in Diabetes ■ Select most appropriate treatment regimens for sample patients based on diabetic presentation and co-morbid conditions ■ Evaluate new products to the market for the treatment of diabetes, including place in therapy, pros and cons of use, major adverse effects, and other pertinent pharmacokinetic and pharmacodynamic properties. SOC-36238233 Socrative Join Code Which of the following correctly pairs a basal insulin and GLP1-RA coformulation? A. Insulin glargine- semaglutide B. Insulin determir- dulaglutide C. Insulin degludec- liraglutide Which new agent was accepted by the FDA for regulatory filing as a dual inhibitor of SGLT-2 in the treatment of type 1 diabetes? A. Sotagliflozin B. Empagliflozin C. Dapagliflozin D. Canagliflozin Under the ADA Standards of Care 2018, a patient with a history of a myocardial infarction would be recommended for which class of medication in addition to metformin? A. Thiazolidinediones B. Sulfonylureas C. Sodium Glucose Co-Transporter 2 Inhibitor D. Alpha Glucosidase Inhibitor Under the updated guidelines of the American Association of Clinical Endocrinologists, a patient failing to achieve A1C goal with metformin would be most appropriately treated with a medication from which class? A. Glucagon-like Peptide 1 Receptor Agonist B. Meglitinides C. Bolus insulin D. Amylin Analog Diabetes in America ■ According to the CDC, more than 30 million Americans have diabetes – 1 in 4 don’t even know – Total direct and indirect cost is more than $240 billion/year – Seventh leading cause of death in the United States in 2015 ■ According to the American Diabetes Association, 1 in 3 Americans has prediabetes – That's more than 84 million Americans! – 90% of these patients do not know their risk https://www.cdc.gov/diabetes/basics/quick-facts.html National Diabetes Statistics Report, 2017 Diabetes in America ■ In the last 20 years, the number of diagnosed cases of diabetes has tripled as the population has aged CDC's Division of Diabetes Translation. United States Diabetes Surveillance System. http://www.cdc.gov/diabetes/data Diabetes in America Sotagliflozin Dapagliflozin/metformin Lixisenatide *Pending approval 10/2014 7/2016 2019 dapagliflozin/saxagliptin empagliflozin/metformin 2/2017 8/2015 Insulin degludec/liraglutide Empagliflozin/linagliptin Insulin glargine/lizisenatide 2/2015 11/2016 Semaglutide Ertugliflozin Insulin degludec Ertugliflozin/metformin Insulin degludec/insulin aspart Ertugliflozin/sitagliptin 9/2015 12/2017 NEW MEDICATIONS NEW INDICATIONS ■ Regular Insulin U-500 Pen ■ Insulin Lispro U-200 Pen Insulin and Insulin Changes ■ Insulin Glargine U-300 Pen ■ Insulin Degludec (Tresiba) Regular Insulin U-500 Pen ■ Class – Regular Insulin (Humulin-R) ■ Delivery Method – Kwikpen – U-500 syringes ■ Clinical Pearls – Useful for severely insulin-resistant patients requiring >200 units/day – Contains both basal and prandial properties ■ Can be used as monotherapy ■ Requires 2-3 injections per day – Can reduce insulin volume by 80% compared to U-100 Regular Insulin U-500 Vial and Syringe Pen ■ Syringe calibrated for 500U/1ML ■ Dial doses in increments of 5 units ■ No conversion needed ■ No conversion needed ■ Reduced risk for dosing errors ■ Reduced risk for dosing errors ■ Use with 20ml vial ■ Ease of administration with pens ■ 1500 units/3 ml pen, 2 pens per box https://www.humulin.com/hcp/delivery-options.aspx#u-500-kwikpen Insulin Lispro U-200 Pen ■ Class – Rapid Acting Insulin (Humalog) ■ Delivery Method – 200 units/1ml pen, can dial doses in 1-unit increments – Max dose per injection is 60 units – Box contains 2 x 3ml pens ■ Clinical Pearls – Rapid-acting meal time insulin given 15 minutes before a meal – One-half the volume of U-100 insulins – Consider switching when meal time insulin needs >20 units/meal – No dosing conversion needed from U-100 to U-200 https://www.humalog.com/hcp/humalog-u200/ Insulin Lispro Junior Pen ■ Class – Rapid acting insulin (Humalog Junior) ■ Delivery Method – Insulin lispro pen device delivering 0.5-unit increments! ■ Clinical Pearls – Self- contained delivery unit only requiring an additional pen needle – Can dial between 0.5 units and 30 units per injection https://www.humalog.com/hcp/humalog-u100-and-junior-kwikpen/#junior_kwikpen Insulin Lispro U-100 ■ Class - Rapid-acting insulin (Admelog) ▪ "Follow on" to Humalog ■ Delivery Method - Available in Solostar or vial ▪ Discard open insulin after 28 days ■ Clinical Pearls - Identical amino acid sequence to Eli Lilly insulin lispro leading to similar PK profile - 1:1 dosing conversion from other insulin lispro products - ADE: similar to other rapid acting insulins- hypoglycemia, hypokalemia, lipodystrophy Insulin Aspart U-100 ■ Class – Rapid-acting insulin (Fiasp) ■ Delivery Method – Available in Flextouch or vial ▪ Max 80 units per injection with pen ▪ Discard open insulin after 28 days ■ Clinical Pearls – Insulin aspart with two excipients allowing ultra-rapid acting characteristics ▪ Enters blood stream in ~2.5 minutes ▪ Can be taken with start of meal or within 20 minutes of starting – 1:1 dosing conversion from other rapid acting insulin products – Not approved for pediatric population – ADE: similar to other rapid acting insulins- hypoglycemia, hypokalemia, lipodystophy Insulin Glargine U-300 Pen ■ Class – Basal insulin (Toujeo Max Solostar) ■ Delivery Method – Same insulin glargine U-300 in original pen device – Pen device has changed to hold 900 units of insulin per pen – Packages as 2 x 3ml pens – Dose 2-160 units per injection ■ Clinical Pearls – Insulin glargine U-100 to U-300 conversion- 1:1 – 42-day expiration after opening, removal from refrigeration Insulin Degludec ■ Class – Basal Insulin (Tresiba) ■ Delivery Method – Available as U-100 or U-200 insulin pens ■ Clinical Pearls – Unique PK: T ½ 25 hours ■ Provides 42-hour coverage ■ Allows for a more flexible dosing schedule – 1:1 dose conversion from other basal or intermediate insulins – Insulin naïve patients: start with 10 units nightly DEVOTE Trial ■ Non-inferiority safety outcomes trial in risk of major cardiovascular events (MACE) with insulin degludec U-100 compared to insulin glargine U-100 ■ Treat to target study design of 7600+ patients with inadequately controlled diabetes and atherosclerotic cardiovascular disease ■ Primary endpoint: time to first MACE – 8.5% in degludec group vs 9.3% in glargine group ■ Secondary confirmatory endpoint: number and incidence of severe hypoglycemic events Insulin degludec/ insulin aspart ■ Class – basal insulin/ rapid acting insulin combination (Ryzodeg) ■ Delivery Method – Available in Flextouch pens – 0.7 units insulin degludec and 0.3 units insulin aspart in each 1 unit of insulin ■ Clinical Pearls – Unlike other mix insulins, solution should be clear and cloudless – Titrate to goal basal dosing- may need to supplement bolus doses ■ Place in Therapy (PiT): reduce needle sticks by combining injections ■ Samaglutide New Non-insulin ■ Lixisenatide Therapies ■ Sotagliflozin ■ Ertugliflozin Semaglutide injection ■ Class – Glucagon-like peptide-1 receptor agonist (Ozempic) ■ Delivery Method – Different pens for 0.25 and 0.5mg doses vs 1mg doses – Dosing ■ 0.25mg SQ weekly x 4 weeks ■ Week 5: Increase to 0.5mg SQ weekly ■ Week 9: May increase to 1mg SQ weekly ■ Clinical Pearls – Take missed dose if remember within 5 days – Adverse Drug Effects (ADE): Nausea, vomiting, diarrhea, abdominal pain, constipation – Warnings: possible thyroid tmors, including cancer Semaglutide injection ■ Semaglutide outperformed dulaglutide in head-to-head A1C lowering (SUSTAIN 7) – 40 weeks, randomized, open-label, active control of 1201 adults – Semaglutide 0.5mg vs dulaglutide 0.75mg ■ A1C lowered 1.4% vs 1.1% (baseline 8.2 vs 8.3) – Semaglutide 1mg vs dulaglutide 1.5mg ■ A1C lowered 1.6% vs 1.3% (baseline 8.2) ■ Semaglutide outperfomed sitagliptan and exenatide extended release in head-to-head A1C lowering (SUSTAIN 2 & SUSTAIN 3) Semaglutide Injection ■ Semaglutide was evaluated for CV safety in a 2-year cardiovascular outcomes trial (CVOT) ■ SUSTAIN 6- 104 week, randomized, multinational, multicenter, double blind, placebo controlled, parallel group, noninferiority, CV safety trial of 3297 adults – Randomized 1:1:1:1 to semaglutide 0.5mg or 1 mg or plaecbo 0.5 or 1mg – All received Diabetes and cardiovascular standards of care – Primary endpoint: first occurance of MACE ■ Standard of care: 8.9% ■ Semaglutide: 6.6% ■ No additional clinical studies establishing reduction in MACE Lixisenatide Injection ■ Class – GLP-1 Receptor Antagonist (Adlyxin in US, Lyxumia in EU) ■ Delivery Method – Dosing: Starter pack of 10 mcg SQ daily for 14 days then increase to 20 mcg SQ daily (Starter pack contains one 10mcg pen and one 20mcg pen) – Maintenance pack contains two 20mcg pens ■ Clinical Pearls – MACE: no reduction shown – Similar ADE and warnings to other members of the class Sotagliflozin ■ FDA has accepted regulatory filing with a target action date of March 2019 ■ Class – Oral dual inhibitor of SGLT-1 and
Load more

Recommended publications
  • Semaglutide Versus Liraglutide for Treatment of Obesity
    Archives of Diabetes & Obesity DOI: 10.32474/ADO.2021.03.000162 ISSN: 2638-5910 Review Article Semaglutide versus liraglutide for treatment of obesity Nasser Mikhail* *Department of Medicine, Endocrinology Division, David-Geffen UCLA Medical School, USA *Corresponding author: Nasser Mikhail, Endocrinology Division, Department of Medicine, Olive View-UCLA Medical Center, David- Geffen UCLA Medical School, CA, USA Received: April 02, 2021 Published: April 19, 2021 Abstract Background: Once weekly (OW) semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under evaluation for treatment of obesity at a dose of 2.4 mg OW. Objective Methods : To compare weight-loss efficacy and safety of once daily (OD) liraglutide 3.0 mg versus OW semaglutide 2.4 mg. : Pubmed research up to March 31, 2021. Randomized trials, pertinent animal studies, and reviews are included. Search Results terms were glucagon-like peptide-1 receptor agonists, weight loss, obesity, liraglutide, semaglutide, efficacy, safety. semaglutide 2.4 mg. However, marked resemblance between trials in terms of study protocols and subjects’ characteristics may allow indirect: No comparison. head to head In clinical trials are trials available of OW tosemaglutide, provide direct this comparison drug was consistently of efficacy ofassociated OD liraglutide with greater 3.0 mg weightversus lossOW than in trials of OD liraglutide. Thus, placebo-corrected percentage weight reduction was -10.3 to -12.4% and -5.4% with OW semaglutide and OD liraglutide, respectively. In patients with type 2 diabetes, corresponding weight reduction was less pronounced with both drugs being -6.2% and -4.3% with OW semaglutide and OD liraglutide, respectively.
    [Show full text]
  • GLP-1 Receptor Agonists
    Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-in- development, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm) for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. GLP-1 Receptor Agonists Evidence Summary GLP-1 agonists are beneficial for patients with type 2 diabetes and obesity. Some evidence suggests benefits for Alzheimer’s disease. It is unclear whether it is beneficial for individuals without underlying metabolic disease. Semaglutide seems to be most effective for metabolic dysfunction, though liraglutide has more preclinical data for Alzheimer’s disease. Neuroprotective Benefit: Evidence from many preclinical studies and a pilot biomarker study suggest some neuroprotective benefits with GLP-1 agonists. However, whether they may be beneficial for everyone or only a subset of individuals (e.g. diabetics) is unclear. Aging and related health concerns: GLP-1 agonists are beneficial for treating diabetes and cardiovascular complications relating to diabetes. It is not clear whether they have beneficial effects in otherwise healthy individuals. Safety: GLP-1 agonists are generally safe for most people with minor side effects. However, long-term side effects are not known. 1 Availability: Available Dose: Varies - see Chemical formula: C172H265N43O51 (Liraglutide) as a prescription chart at the end of MW: 3751.262 g/mol medicine.
    [Show full text]
  • LANTUS® (Insulin Glargine [Rdna Origin] Injection)
    Rev. March 2007 Rx Only LANTUS® (insulin glargine [rDNA origin] injection) LANTUS® must NOT be diluted or mixed with any other insulin or solution. DESCRIPTION LANTUS® (insulin glargine [rDNA origin] injection) is a sterile solution of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting (up to 24-hour duration of action), parenteral blood-glucose-lowering agent. (See CLINICAL PHARMACOLOGY). LANTUS is produced by recombinant DNA technology utilizing a non- pathogenic laboratory strain of Escherichia coli (K12) as the production organism. Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Chemically, it is 21A- B B Gly-30 a-L-Arg-30 b-L-Arg-human insulin and has the empirical formula C267H404N72O78S6 and a molecular weight of 6063. It has the following structural formula: LANTUS consists of insulin glargine dissolved in a clear aqueous fluid. Each milliliter of LANTUS (insulin glargine injection) contains 100 IU (3.6378 mg) insulin glargine. Inactive ingredients for the 10 mL vial are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, 20 mcg polysorbate 20, and water for injection. Inactive ingredients for the 3 mL cartridge are 30 mcg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, and water for injection. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide. LANTUS has a pH of approximately 4. CLINICAL PHARMACOLOGY Mechanism of Action: The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism.
    [Show full text]
  • 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]
  • Insulin Aspart Sanofi, If It Is Coloured Or It Has Solid Pieces in It
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Insulin aspart Sanofi 100 units/ml solution for injection in vial Insulin aspart Sanofi 100 units/ml solution for injection in cartridge Insulin aspart Sanofi 100 units/ml solution for injection in pre-filled pen 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One ml solution contains 100 units insulin aspart* (equivalent to 3.5 mg). Insulin aspart Sanofi 100 units/ml solution for injection in vial Each vial contains 10 ml equivalent to 1,000 units insulin aspart. Insulin aspart Sanofi 100 units/ml solution for injection in cartridge Each cartridge contains 3 ml equivalent to 300 units insulin aspart. Insulin aspart Sanofi 100 units/ml solution for injection in pre-filled pen Each pre-filled pen contains 3 ml equivalent to 300 units insulin aspart. Each pre-filled pen delivers 1-80 units in steps of 1 unit. *produced in Escherichia coli by recombinant DNA technology. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for injection (injection). Clear, colourless, aqueous solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Insulin aspart Sanofi is indicated for the treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above. 4.2 Posology and method of administration Posology The potency of insulin analogues, including insulin aspart, is expressed in units, whereas the potency of human insulin is expressed in international units.
    [Show full text]
  • 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.
    [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]
  • Think Medicines!
    Think Issue 13 August 2016 MHRA Drug Safety SGLT2 inhibitors: updated advice on the risk of diabetic Medicines!Updates can be found ketoacidosis (DKA) at the following link. The MHRA are advising health care professionals to test for raised ketones in patients with ketoacidosis symptoms, who are taking SGLT2 inhibitors even if New higher strength Humalog® plasma glucose levels are near-normal. SGLT2 inhibitors include: Canagliflozin, 200 units/ml KwikPen™ Dapagliflozin and Empagliflozin. Serious, life-threatening, and fatal cases of In order to minimize medication DKA have been reported in patients taking an SGLT2 inhibitor. In several cases, errors. blood glucose levels were only moderately elevated (e.g. <14mmol/L) Insulin lispro 200 units/ml representing an atypical presentation for DKA, which could delay diagnosis and solution for injection should treatment. ONLY be administered using the Advice for health Care Professionals: Humalog 200 units/ml pre-filled Inform patients of the signs of diabetic ketoacidosis (DKA) and advise them to pen (KwikPen). seek immediate medical advice if they develop any of these symptoms (e.g. When switching from one rapid weight loss, feeling sick or being sick, stomach pain, fast and deep Humalog strength to another, breathing, sleepiness, a sweet smell to the breath, a sweet or metallic taste in the dose does not need to be the mouth, or a different odour to urine or sweat). converted. Unnecessary dose Discuss the risk factors of DKA with patients. conversion may lead to under/ Discontinue treatment with the SGLT2 inhibitor immediately if DKA is over dosing and resultant hyper/ suspected or diagnosed.
    [Show full text]
  • Supplementary Material
    Supplementary material Table S1. Search strategy performed on the following databases: PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL). 1. Randomi*ed study OR random allocation OR Randomi*ed controlled trial OR Random* Control* trial OR RCT Epidemiological study 2. sodium glucose cotransporter 2 OR sodium glucose cotransporter 2 inhibitor* OR sglt2 inhibitor* OR empagliflozin OR dapagliflozin OR canagliflozin OR ipragliflozin OR tofogliflozin OR ertugliflozin OR sotagliflozin OR sergliflozin OR remogliflozin 3. 1 AND 2 1 Table S2. Safety outcomes of empagliflozin and linagliptin combination therapy compared with empagliflozin or linagliptin monotherapy in treatment naïve type 2 diabetes patients Safety outcome Comparator 1 Comparator 2 I2 RR [95% CI] Number of events Number of events / / total subjects total subjects i. Empagliflozin + linagliptin vs empagliflozin monotherapy Empagliflozin + Empagliflozin linagliptin monotherapy ≥ 1 AE(s) 202/272 203/270 77% 0.99 [0.81, 1.21] ≥ 1 drug-related 37/272 38/270 0% 0.97 [0.64, 1.47] AE(s) ≥ 1 serious AE(s) 13/272 19/270 0% 0.68 [0.34, 1.35] Hypoglycaemia* 0/272 5/270 0% 0.18 [0.02, 1.56] UTI 32/272 25/270 29% 1.28 [0.70, 2.35] Events suggestive 12/272 13/270 9% 0.92 [0.40, 2.09] of genital infection i. Empagliflozin + linagliptin vs linagliptin monotherapy Empagliflozin + Linagliptin linagliptin monotherapy ≥ 1 AE(s) 202/272 97/135 0% 1.03 [0.91, 1.17] ≥ 1 drug-related 37/272 17/135 0% 1.08 [0.63, 1.84] AE(s) ≥ 1 serious AE(s) 13/272 2/135 0% 3.22 [0.74, 14.07] Hypoglycaemia* 0/272 1/135 NA 0.17 [0.01, 4.07] UTI 32/272 12/135 0% 1.32 [0.70, 2.49] Events suggestive 12/272 4/135 0% 1.45 [0.47, 4.47] of genital infection RR, relative risk; AE, adverse event; UTI, urinary tract infection.
    [Show full text]
  • A Critical Appraisal of the Role of Insulin Analogues in the Management of Diabetes Mellitus Ralph Oiknine, Marla Bernbaum and Arshag D
    Drugs 2005; 65 (3): 325-340 REVIEW ARTICLE 0012-6667/05/0003-0325/$39.95/0 2005 Adis Data Information BV. All rights reserved. A Critical Appraisal of the Role of Insulin Analogues in the Management of Diabetes Mellitus Ralph Oiknine, Marla Bernbaum and Arshag D. Mooradian Division of Endocrinology, Department of Internal Medicine, Diabetes, and Metabolism, St Louis University School of Medicine, St Louis, Missouri, USA Contents Abstract ....................................................................................325 1. Physiology of Insulin Secretion .............................................................326 2. Conventional Insulin Preparations ..........................................................327 3. Insulin Analogues ........................................................................328 3.1 Rapid-Acting Insulin Analogues .......................................................328 3.1.1 Insulin Lispro ...................................................................328 3.1.2 Insulin Aspart ..................................................................329 3.1.3 Insulin Glulisine .................................................................329 3.1.4 Clinical Utility of Rapid-Acting Insulin Analogues ...................................330 3.2 Premixed Insulins and Insulin Analogues ................................................331 3.3 Basal Insulin Analogues ...............................................................331 3.3.1 Insulin Glargine ................................................................331
    [Show full text]
  • Steglujan, INN-Ertugliflozin-Sitagliptin
    25 January 2018 EMA/86941/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report Steglujan International non-proprietary name: ertugliflozin / sitagliptin Procedure No. EMEA/H/C/004313/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2018. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion ................................................................................ 9 2.1. Problem statement ............................................................................................... 9 2.1.1. Disease or condition ........................................................................................... 9 2.1.2. Epidemiology .................................................................................................... 9 2.1.3. Clinical presentation ..........................................................................................
    [Show full text]
  • 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.
    [Show full text]