New Medications for the Treatment of Diabetes
2018; Mary Ann Liebert, Inc.; Volume: 20; Issue: S1 Linguagem: Inglês
10.1089/dia.2018.2512
ISSN1557-8593
AutoresSatish K. Garg, Amanda Rewers, Halis Kaan Aktürk,
Tópico(s)Pancreatic function and diabetes
ResumoDiabetes Technology & TherapeuticsVol. 20, No. S1 Original ArticlesFree AccessNew Medications for the Treatment of DiabetesSatish K. Garg, Amanda H. Rewers, and H. Kaan AkturkSatish K. GargBarbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado.Search for more papers by this author, Amanda H. RewersBarbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado.Search for more papers by this author, and H. Kaan AkturkBarbara Davis Center for Diabetes, University of Colorado, Aurora, Colorado.Search for more papers by this authorPublished Online:1 Feb 2018https://doi.org/10.1089/dia.2018.2512AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail IntroductionThere is currently a worldwide epidemic of diabetes, primarily type 2, affecting nearly half a billion people. The data also show that improving glucose control reduces long-term complications of diabetes; thus, researchers are always finding new pathways to improve diabetes outcomes to reduce the overall burden of diabetes. Unfortunately, the cost of caring for diabetes (which includes medications, outpatient and inpatient care, and long-term complications) keeps going up. During the past year, from July 2016 to June 2017, we reviewed several abstracts and manuscripts from PubMed and chose those listed below for our article.Key Articles Reviewed for the ArticleA randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1Garg S, Dreyer M, Jinnouchi H, Mou J, Qu Y, Hartman ML, Rosilio M, Jacober SJ, Bastyr EJ 3rd; for IMAGINE 1 Trial InvestigatorsDiabetes Obes Metab 2016;18(Suppl 2): 25–33Basal insulin peglispro: overview of a novel long-acting insulin with reduced peripheral effect resulting in a hepato-preferential actionJacober SJ, Prince MJ, Beals JM, Hartman ML, Qu Y, Linnebjerg H, Garhyan P, Haupt ADiabetes Obes Metab 2016;18(Suppl 2): 3–16A novel option for prandial insulin therapy: inhaled insulinDailey G, Ahmad A, Polsky S, Shah VPostgrad Med 2016;128: 839–847Inhaled insulin: a clinical and historical reviewChan J, Cheng-Lai ACardiol Rev 2017;25: 140–146Place of technosphere inhaled insulin in treatment of diabetesMikhail NWorld J Diabetes 2016;7: 599–604Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulinHeinemann L, Baughman R, Boss A, Hompesch MJ Diabetes Sci Technol 2017;11: 148–156Effect of insulin degludec versus insulin glargine on glycemic control and daily fasting blood glucose variability in insulin-naïve Japanese patients with type 2 diabetes: I'D GOT trialAso Y, Suzuki K, Chiba Y, Sato M, Fujita N, Takada Y, Murano S, Kuroda HDiabetes Res Clin Pract 2017;130: 237–243Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspectiveMezquita-Raya P, Darbà J, Ascanio M, Ramírez de Arellano AExpert Rev Pharmacoecon Outcomes Res 2017;17: 587–595Efficacy and safety of degludec versus glargine in type 2 diabetesMarso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, Pratley RE, Haahr PM, Lange M, Brown-Frandsen K, Moses A, Skibsted S, Kvist K, Buse JB; for the DEVOTE Study GroupN Engl J Med 2017;347: 723–732Efficacy and safety of once-daily insulin degludec/insulin aspart versus insulin glargine (U100) for 52 weeks in insulin-naïve patients with type 2 diabetes: a randomized controlled trialKumar A, Franek E, Wise J, Niemeyer M, Mersebach H, Simó RPLoS ONE 2016;11: e0163350Efficacy and safety of insulin degludec for hyperglycemia management in noncritical hospitalized patients with diabetes: an observational studySimioni N, Filippi A, Scardapane M, Nicolucci A, Rossi MC, Frison VDiabetes Ther 2017;8: 941–946LAPSInsulin115: A novel ultra-long-acting basal insulin with a unique action profileWronkowitz N, Hartmann T, Görgens SW, Dietze-Schroeder D, Indrakusuma I, Choi IY, Park SH, Lee YM, Kwon SC, Kang Y, Hompesch M, Eckel JDiabetes Obes Metab 2017;19: 1722–1731Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USAHunt B, Mocarski M, Valentine WJ, Langer JJ Med Econ 2017;20: 663–670A fixed ratio combination of insulin degludec and liraglutide (IDegLira) reduces glycemic fluctuation and brings more patients with type 2 diabetes within blood glucose target rangesKing AB, Philis-Tsimikas A, Kilpatrick ES, Langbakke IH, Begtrup K, Vilsbøll TDiabetes Technol Ther 2017;19: 255–264Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with type 2 diabetes: the DUAL IV trialRodbard HW, Bode BW, Harris SB, Rose L, Lehmann L, Jarlov H, Thurman J; on behalf of Dual Action of Liraglutide and insulin degludec (DUAL) IV trial investigatorsDiabet Med 2017;34: 189–196Lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist for the treatment of adults with type 2 diabetesTrujillo JM, Goldman JPharmacotherapy 2017;37: 927–943Efficacy of additional canagliflozin administration to type 2 diabetes patients receiving insulin therapy: examination of diurnal glycemic patterns using continuous glucose monitoring (CGM)Matsumura M, Nakatani Y, Tanka S, Aoki C, Sagara M, Yanagi K, Suzuki K, Aso YDiabetes Ther 2017;8: 821–827Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): results of a 16-week randomized, double-blind, placebo-controlled multicentre trialTerauchi Y, Tamura M, Senda M, Gunji R, Kaku KDiabetes Obes Metab 2017;19: 1397–1407Preventive effect of ipragliflozin on nocturnal hypoglycemia in patients with type 2 diabetes treated with basal-bolus insulin therapy: an open-label, single-center, parallel, randomized control studyOkajima F, Nagamine T, Nakamura Y, Hattori N, Sugihara H, Emoto NJ Diabetes Investig 2017;8: 341–345Sodium–glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes: a review of US FDA data and possible conclusionsD'Elia JA, Segal AR, Bayliss GP, Weinrauch LAInt J Nephrol Renovasc Dis 2017;10: 153–158Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot studyFukuda T, Bouchi R, Terashima M, Sasahara Y, Asakawa M, Takeuchi T, Nakano Y, Murakami M, Minami I, Izumiyama H, Hashimoto K, Yoshimoto T, Ogawa YDiabetes Ther 2017;8: 851–861Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulinChamarthi B, Cincotta AHPostgrad Med 2017;129: 446–455Effects of cabergoline on blood glucose levels in type 2 diabetic patients: a double-blind controlled clinical trialBahar A, Kashi Z, Daneshpour E, Akha O, Ala SMedicine 2016;95: 40(e4818)A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1Garg S1, Dreyer M2, Jinnouchi H3, Mou J4, Qu 4, Hartman ML4, Rosilio M4, Jacober SJ4, Bastyr EJ 3rd4,5; for the IMAGINE 1 Trial Investigators1Barbara Davis Center for Diabetes, University of Colorado Health Sciences Center, Aurora, CO2Wuxi Mingci Cardiovascular Hospital, Wuxi, China3Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan4Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN5Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, INDiabetes Obes Metab 2016;18(Suppl 2): 25–33AimsThe objective of this phase 3 study was to compare basal insulin peglispro (BIL) with insulin glargine (GL) to demonstrate that BIL is noninferior for hemoglobin A1c (HbA1c) at 26 weeks with a noninferiority margin of 0.4%.Material and MethodsIMAGINE 1 was a randomized, open-label, parallel-arm study conducted in adults with type 1 diabetes (n=455). Participants in nine countries were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. Data capture and insulin dosing calculations for intensive insulin management were facilitated by an electronic diary.ResultsFor patients assigned to BIL (n=295) and GL (n=160), mean HbA1c at 26 weeks was 7.06 ±0.04% and 7.43±0.06% respectively (difference −0.37% [95% confidence interval −0.50 to −0.23], P<.001). More patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P<.001). Patients using BIL lost weight, with 36% less nocturnal hypoglycemia, 29% more total hypoglycemia, more severe hypoglycemia, and lower fasting serum glucose and between-day fasting blood glucose variability compared with those using GL. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3× upper limit of normal (ULN). Treatment with BIL was associated with more frequent injection site reactions and an increase in serum triglycerides from baseline levels.ConclusionsIn patients with type 1 diabetes, treatment with BIL compared with GL for 26 weeks was associated with weight loss, lower glucose variability, lower HbA1c, and less nocturnal hypoglycemia. Increases in total and severe hypoglycemia, triglycerides, aminotransferases, and injection site reactions were also noted.Basal insulin peglispro: overview of a novel long-acting insulin with reduced peripheral effect resulting in a hepato-preferential actionJacober SJ, Prince MJ, Beals JM, Hartman ML, Qu Y, Linnebjerg H, Garhyan P, Haupt AEli Lilly and Company, Indianapolis, INDiabetes Obes Metab 2016;18(Suppl 2): 3–16IntroductionBasal insulin peglispro (BIL) is a novel basal insulin with a flat, prolonged activity profile. BIL has been shown to have significant hepato-preferential action as a result of reduced peripheral activity in a dog model and in healthy men, as well as in patients with type 1 diabetes (T1D).Materials and MethodsThe IMAGINE–phase 3 clinical trial program included more than 6000 patients; ∼3900 of them received BIL. Of seven pivotal IMAGINE trials, three studies were double-blinded and three were in T1D patients.ResultsAcross the studies, BIL consistently demonstrated less glycemic variability, a greater HbA1c reduction, and a clinically relevant reduction in the rates of nocturnal hypoglycemia across comparator [glargine and isophane insulin] studies. Trials that employed basal/bolus regimens reported higher rates of total hypoglycemia with BIL due to higher rates of daytime hypoglycemia. Severe hypoglycemia rates among patients with T1D and those with type 2 diabetes (T2D) were similar to comparator studies. T1D patients lost weight and T2D patients tended to gain less weight with BIL compared with glargine. BIL was also associated with higher liver fat, triglycerides, and alanine aminotransferase (ALT) levels, including a higher frequency of ALT elevation ≥3 times the upper limit of normal, but without severe, acute drug-induced liver injury. Injection site reactions, primarily lipohypertrophy, were more frequent with BIL.ConclusionsRelative to conventional comparator insulin, BIL demonstrated better glycemic control with reduced glucose variability and nocturnal hypoglycemia but higher triglycerides, ALT, and liver fat. The hepato-preferential action of BIL with reduced peripheral activity may account for these findings.A novel option for prandial insulin therapy: inhaled insulinDailey G1, Ahmad A1, Polsky S2, Shah V21Division of Diabetes & Endocrinology, Scripps Clinic, La Jolla, CA2Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, COPostgrad Med 2016;128: 839–847Many adults with type 2 diabetes (T2D) are unable to achieve or maintain glycemic targets using only oral antidiabetes drugs (OADs) and therefore require insulin therapy. It is common to begin basal insulin when more intensive treatment becomes a necessity; however, individualized therapy (within current guidelines) for treatment of postprandial hyperglycemia may lead more health-care professionals (HCPs) to add rapid-acting insulin (RAI) to OAD regimens to achieve glycated hemoglobin (HbA1c) targets. The burden associated with injections is a concern to both HCPs and patients. As an alternative to injectable bolus doses of prandial insulin, inhaled Technosphere insulin (inhaled TI) has the potential to increase patient and HCP willingness to intensify therapy and improve compliance with more complex regimens. Clinical studies of inhaled TI have shown it to be well tolerated and effective as a prandial insulin for adults with T2D, offering the potential to improve both treatment satisfaction and quality of life. Inhaled TI provides a very rapid onset of action and a short duration of antihyperglycemic effect, which may reduce the risk of insulin stacking (overlapping effects of RAI injections taken <4 hours apart) and postprandial hypoglycemia. This review presents inhaled TI as an alternative to OADs or injected insulin as adjunctive therapy that warrants consideration by HCPs and patients striving to achieve glycemic targets.Inhaled insulin: a clinical and historical reviewChan J1, Cheng-Lai A1Department of Pharmacy, Montefiore Medical Center, Bronx, NYCardiol Rev 2017;25: 140–146Insulin, a cornerstone of diabetes management, is the most effective blood glucose lowering agent available, yet many patients are either reluctant to begin or are nonadherent to insulin therapy due to fear of frequent injections and other various reasons. Technosphere insulin (TI) is a novel inhaled insulin powder approved by the U.S. Food and Drug Administration for the management of diabetes. In two phase 3 clinical trials TI was shown to be noninferior to subcutaneous insulin aspart and superior to inhaled placebo in lowering HbA1c in patients with type 1 and type 2 diabetes mellitus, respectively. TI appears to be generally well tolerated across both studies; the most common adverse effects were hypoglycemia and cough. However, additional studies are needed to address safety concerns regarding long-term pulmonary effects. Overall, for individuals with diabetes who are at risk for medication nonadherence due to aversion to frequent injections, TI appears to be a promising noninvasive prandial insulin alternative. This article reviews the historical development of TI, data regarding its safety and efficacy, and its advantages and disadvantages over traditional injectable insulins.Place of technosphere inhaled insulin in treatment of diabetesMikhail NDepartment of Medicine, OliveView-UCLA Medical Center, Sylmar, CAWorld J Diabetes 2016;7: 599–604Technosphere insulin (TI), Afrezza, is an orally inhaled powder form of short-acting regular insulin. Taken with meals, the action of TI peaks approximately 40–60 min after inhalation and lasts for 2–3 h. TI is slightly less effective than subcutaneous insulin aspart, with mean HbA1c reduction of 0.21% and 0.4%, respectively. When effect on HbA1c levels was compared between TI and technosphere inhaled placebo, the decrease was 0.8% and 0.4% respectively. Compared with insulin aspart, TI is associated with lower risk of late postprandial hypoglycemia and weight gain. Cough is reported by 24%–33% of TI patients, vs. 2% with insulin aspart, making it the most common adverse effect of TI after hypoglycemia. TI is contraindicated in patients with asthma and chronic obstructive pulmonary disease. TI is an attractive option of prandial insulin; however, its use is limited by frequent occurrence of cough, the need for periodic monitoring of pulmonary function, and a lack of long-term safety data. Patients experiencing frequent hypoglycemia while using short-acting subcutaneous insulin, particularly late postprandial hypoglycemia, patients with needle phobia, and those who cannot tolerate subcutaneous insulin due to skin reactions are candidates for use of TI.Pharmacokinetic and pharmacodynamic properties of a novel inhaled insulinHeinemann L1, Baughman R2, Boss A3, Hompesch M41Science & Co, Düsseldorf, Germany2MannKind Corporation, Danbury, CT3Sanofi, Bridgewater, NJ4Profil Institute for Clinical Research, San Diego, CAJ Diabetes Sci Technol 2017;11: 148–156In recent decades, advances in insulin treatment options have markedly improved the management of diabetes. However, glycemic control remains suboptimal for many people with diabetes. Although the development of subcutaneously injected rapid-acting insulin analogs has improved postprandial glucose control, currently available insulins are not capable of fully mimicking the physiological time-action profile of postmeal, endogenously secreted insulin. The delayed start of metabolic action and prolonged period of effect of these insulins induce the risk of postprandial hyperglycemia and late postprandial hypoglycemia. Several alternative routes of administration have been investigated in an attempt to provide an improved time-action insulin profile that more closely simulates physiological prandial insulin release and to overcome the limitations associated with subcutaneous administration. Among these, pulmonary insulin delivery has shown the most promise, and the U.S. Food and Drug Administration (FDA) recently approved Technosphere® insulin (TI), a rapid-acting inhaled human insulin, for prandial insulin therapy. This article presents the pharmacokinetic and pharmacodynamic properties of TI and the implications for improved postprandial glucose control based on key studies carried out during its clinical development.Effect of insulin degludec versus insulin glargine on glycemic control and daily fasting blood glucose variability in insulin-naïve Japanese patients with type 2 diabetes: I'D GOT trialAso Y1, Suzuki K1, Chiba Y2, Sato M3, Fujita N4, Takada Y5, Murano S6, Kuroda H71Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan2Nagasaki Hospital, Ashikaga, Tochigi, Japan3National Hospital Organization Utsunomiya National Hospital, Utsunomiya, Tochigi, Japan4Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan5Takada Clinic, Tochigi, Tochigi, Japan6Tochigi Medical Center Shimotsuga, Tochigi, Tochigi, Japan7Green Clinic, Mibu, Tochigi, JapanDiabetes Res Clin Pract 2017;130: 237–243AimsInsulin degludec (IDeg) is an ultra-long-acting insulin with a smooth time/action profile over more than 42 h. The effects of IDeg and insulin glargine (IGlar) on both HbA1c reduction and within-subject day-to-day variability of fasting blood glucose (FBG) were examined in insulin-naïve patients with type 2 diabetes.Subjects and MethodsParticipants were randomly assigned to once-daily basal insulin IDeg or IGlar at a 3:1 ratio (n=31 and n=12, respectively). Insulins were administered before breakfast and titrated to achieve a target FBG <110 mg/dL. Change in HbA1c from baseline to 24 weeks of treatment was a primary endpoint, as were the coefficient of variation (CV) and standard deviation (SD) of FBG from 8 to 12 weeks and from 20 to 24 weeks. Secondary endpoints included quality of life (QOL) as evaluated by the Diabetes Therapy-Related QOL questionnaire.ResultsAfter 24 weeks at the same insulin dosage, HbA1c level decreased by 1.6% in the IDeg group and 1.7% in the IGlar group. FBG was significantly lower and the CV of FBG was significantly smaller in the IDeg group than in the IGlar group. The frequency of total and severe hypoglycemic episodes did not differ between the groups. QOL regarding anxiety and dissatisfaction with treatment showed significant improvement in the IDeg group.ConclusionsIn insulin-naïve patients with type 2 diabetes, treatment with IDeg or IGlar achieved similar improvement in glycemic control. The day-to-day variation of FBG was smaller in patients receiving IDeg.Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspectiveMezquita-Raya P1, Darbà J2, Ascanio M3, Ramírez de Arellano A41Hospital Torrecardenas, Clínica San Pedro, Almería, Spain2Department of Economics, Universitat de Barcelona, Barcelona, Spain3Department of Health Economics, BCN Health Economics & Outcomes Research S.L., Barcelona, Spain4HEOR Europe, Novo Nordisk, Madrid, SpainExpert Rev Pharmacoecon Outcomes Res 2017;17: 587–595BackgroundThis study aimed to assess the cost-effectiveness of insulin degludec versus insulin glargine in three groups of patients from the Spanish National Health System (NHS).MethodsA short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment.ResultsDegludec was the dominant strategy for type 2 diabetes mellitus (T2DM) basal only therapy (BOT) and exhibited an incremental cost-effectiveness ratio (cost per quality-adjusted life year [QALY]) of 52.70 €/QALY for T1DM basal/bolus (B/B) and 11,240.88 €/QALY for T2DM B/B. Lower costs are primarily driven by lower nocturnal and severe hypoglycemic events, which were reduced versus IGlar. In all three patient groups, the reduced incidence of hypoglycemic events resulted in improved clinical outcomes, with QALYs showing gains of 0.0211, 0.0328, and 0.0248 when compared with IGlar for T1DM B/B, T2DM BOT, and T2DM B/B, respectively. Incremental cost-effectiveness ratios (ICERs) were stable to plausible variations in the analyzed parameters of different scenario analyses, except when the same number of self-monitoring of blood glucose (SMBGs) were used for both treatments, with T2DM B/B showing an ICER over the accepted threshold.ConclusionsThe results of this analysis demonstrate that degludec, when used in patients currently treated with long-acting insulin, is a cost-effective option in the Spanish NHS.Efficacy and safety of degludec versus glargine in type 2 diabetesMarso SP1, McGuire DK2, Zinman B3, Poulter NR4, Emerson SS5, Pieber TR6, Pratley RE7, Haahr PM8, Lange M8, Brown-Frandsen K8, Moses A8, Skibsted S8, Kvist K8, Buse JB9; for the DEVOTE Study Group1Research Medical Center, Kansas City, MO2University of Texas Southwestern Medical Center, Dallas, TX3Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada4Imperial Clinical Trials Unit, Imperial College London, London, UK5University of Washington, Seattle, WA6Medical University of Graz, Graz, Austria7Florida Hospital Translational Research Institute for Metabolism and Diabetes and Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL8Novo Nordisk, Søborg, Denmark9University of North Carolina School of Medicine, Chapel Hill, NCN Engl J Med 2017;377: 723–732This manuscript is also discussed in the article on New Insulins, Biosimilars, and Insulin Therapy, page S-55.BackgroundDegludec is an ultra-long-acting, once-daily basal insulin approved for use in adults, adolescents, and children with diabetes. In previous open-label studies, patients who received degludec have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia than patients receiving basal insulin glargine. However, there is a lack of data regarding the cardiovascular safety of degludec.MethodsA double-blind, treat-to-target, event-driven cardiovascular outcomes trial was conducted on 7637 patients with type 2 diabetes. Participants were randomly assigned to receive either insulin degludec (n=3818) or insulin glargine U100 (n=3819) once daily between dinner and bedtime. In the time-to-event analysis, the primary composite outcome was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction) with a prespecified noninferiority margin of 1.3. The prespecified, multiplicity-adjusted secondary outcome was adjudicated severe hypoglycemia, as defined by the American Diabetes Association.ResultsOf the 7637 patients in the study, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. Baseline mean age was 65.0 years; mean duration of diabetes, 16.4 years; and the mean (± SD) HbA1c level, 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval 0.78–1.06; P<0.001 for noninferiority). The HbA1c at 24 months was 7.5±1.2% in each group, whereas the mean fasting plasma glucose level was significantly lower in the degludec group than in the glargine group (128±56 vs. 136±57 mg/dL, P<0.001). Prespecified adjudicated severe hypoglycemia occurred in 4.9% (n=187) of patients in the degludec group vs. 6.6% (n=252) in the glargine group, for an absolute difference of 1.7 percentage points (rate ratio, 0.60; P<0.001 for superiority; odds ratio, 0.73; P<0.001 for superiority). There was no difference in rates of adverse events between the two groups.ConclusionsOur study found degludec to be noninferior to glargine among patients with type 2 diabetes at high risk for cardiovascular events with respect to the incidence of major cardiovascular events.Efficacy and safety of once-daily insulin degludec/insulin aspart versus insulin glargine (U100) for 52 weeks in insulin-naïve patients with type 2 diabetes: a randomized controlled trialKumar A1, Franek E2, Wise J3, Niemeyer M4, Mersebach H5, Simó R61Diabetes Care & Research Centre, Near Overbridge, Kankarbagh, Patna, Bihar, India2Medical Research Center, Polish Academy of Sciences and Central Clinical Hospital MSWiA, Warsaw, Poland3Tulane Medical School, Department of Endocrinology, New Orleans, LA4Market Access and Public Affairs, Novo Nordisk Pharma GmbH, Mainz, Germany5Clinical Development & Research-Diabetes & Obesity, Novo Nordisk Inc, Princeton, NJ6Diabetes and Metabolism Research Unit, Autonomous University of Barcelona, Vall d'Hebron Institute de Recerca, and CIBERDEM, Barcelona, SpainPLoS ONE 2016;11: e0163350PurposeThis study investigated the efficacy and safety of once daily (OD) insulin degludec/insulin aspart (IDegAsp) compared with OD insulin glargine U100 (IGlar) in insulin-naïve adults with type 2 diabetes mellitus (T2DM) over 52 weeks.MethodsParticipants in this open-label, parallel-group, treat-to-target trial were randomly assigned (1:1) to receive IDegAsp OD at breakfast (n=266) or IGlar OD as per label (n=264). After the initial 26-week term, participants then entered a 26-week extension phase (IDegAsp OD, n=192; IGlar OD, n=221). Change in HbA1c from baseline to week 26 was the primary endpoint.ResultsMean HbA1c decreased to similar levels in both groups at 26 and 52 weeks. The mean estimated treatment difference after 52 weeks was −0.08% [95% confidence interval −0.26, 0.09], confirming the noninferiority of IDegAsp OD vs. IGlar OD evaluated at week 26. In both treatment groups there was a similar reduction in mean fasting plasma after 52 weeks. The rate of confirmed hypoglycemic episodes was 86% higher (P<0.0001) for IDegAsp than for IGlar, but the rate of nocturnal hypoglycemia was 75% lower (P<0.0001).ConclusionWhile nocturnal-confirmed hypoglycemia was higher with IGlar, overall and diurnal hypoglycemia were higher with IDegAsp dosed at breakfast. These results reinforce the importance of administering IDegAsp with the main meal of the day, tailored to meet individual patient needs.Efficacy and safety of insulin degludec for hyperglycemia management in noncritical hospitalized patients with diabetes: an observational studySimioni N1, Filippi A1, Scardapane M2, Nicolucci A2, Rossi MC2, Frison V11Department of Medicine, Cittadella Hospital, ULSS15 Alta Padovana, Cittadella, Padua, Italy2CORESEARCH, Center for Outcomes Research and Clinical Epidemiology, Pescara, ItalyDiabetes Ther 2017;8: 941–946BackgroundThe efficacy and safety of insulin degludec administered in a basal-bolus regimen according to the GesTIO protocol in noncritical hospitalized patients with type 1 and type 2 diabetes mellitus was assessed.MethodsThe study included 52 subjects (48.1% ≥75 years) managed through a basal-bolus scheme including degludec. Mean blood glucose levels (BGs) and standard deviations (SDs) were calculated and compared at admission vs. discharge. The proportion of patients with BG at target (140–180 mg/dL) or below target at discharge as well as the incidence rate (95% confidence interval) of hypoglycemia were also assessed.ResultsFasting BG decreased between admission and discharge, from 237 to 153 mg/dL (P<0.0001) and SD fell from 125 to 38 mg/dL (P<0.0001). Average BG also dropped, from 189 to 145 mg/dL (SD went from 57 to 32 mg/dL). At discharge 28.9% of participants had BG at target, and 50.0% had levels below target (average 119.0±14.4 mg/dL). The incidence rate of hypoglycemia was 0.07 [0.05–0.11] episodes per person-day, with 1 out of 27 episodes occurring at night.ConclusionsDegludec is effective and minimizes glucose variability and nocturnal hypoglycemia in hospitalized, mainly elderly patients.LAPSInsulin115: a novel ultra-long-acting basal insulin with a unique action profileWronkowitz N1, Hartmann T1, Görgens SW1, Dietze-Schroeder D1, Indrakusuma I1, Choi IY2, Park SH2, Lee YM2, Kwon SC2, Kang Y3, Hompesch M3, Eckel J11Paul-Langerhans-Group, German Diabetes Centre, Düsseldorf, Germany2Hanmi Pharmaceutical, Co., Ltd., Seoul, South Korea3ProSciento, Inc., Chula Vista, CADiabetes Obes Metab 2017;19: 17
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