Abstracts / Can J Diabetes 36 (2012) S24eS76 S57

1.29]).Nocturnalhypoglycemiawassignificantly25% lower for IDegFFvs IGlar (ERR: 0.75 [0.58; 0.97]; p¼0.0255), and severe hypoglycemiawas 26% lower (ERR: 0.74 [0.38; 1.42]). Adverse event rates were lowin both groups. Basal insulin doses did not differ; 0.40 (IDegFF) and0.42 (IGlar) U/kg at 52 weeks. This study demonstrates that IDeg canbe administered flexibly at any time of day with similar glycemiccontrol and less nocturnal hypoglycemia than standard OD IGlargiven at the same time each day over 52 weeks.

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200 U/ml Insulin Degludec Improves Glycemic Control Similarto Insulin Glargine with a Low Risk of Hypoglycemia in Insulin-naïve People with Type 2 DiabetesRICHARD BERGENSTAL, ANUJ BHARGAVA, RAJEEV K. JAIN,STUART A. ROSS*, AZHAR RANA, HENRIETTE MERSEBACH,STEPHEN GOUGHMinneapolis, MN; Des Moines, IA; Milwaukee, WI; Calgary, AB;Søborg, Denmark; Oxford, UK

Insulin degludec (IDeg) is a new basal insulin that has an ultra-long and flat time-action profile with a half-life >42 hours. This 26-week, open-label, treat-to-target trial compared the efficacy andsafety of once-daily IDeg U200 with 100 U/ml of insulin glargine(IGlar). Insulin-naïve patients with type 2 diabetes (T2D) (n¼457;57.5 years old, BMI 32.4 kg/m2, HbA1c 8.3%, and fasting plasmaglucose (FPG) 9.6 mmol/L were randomized to IDeg U200 or IGlar,both given OD in combinationwith metformin� DPP-4 inhibitor inprefilled pen devices. Basal insulin was titrated weekly to a FPGtarget of 4e5 mmol/L. At 26 weeks, IDeg U200 effectively reducedHbA1c by 1.30%- points and was non-inferior to IGlar (estimatedtreatment difference (ETD) IDeg-IGlar: 0.04%-points [95% CI: e0.11;0.19]). FPG reductions were significantly greater with IDeg U200than with IGlar (e3.7 vs. e3.4 mmol/L; ETD: e0.42 [e0.82; e0.06],p¼0.02). Rates of overall confirmed hypoglycemia (PG<3.1 mmol/Lor requiring assistance) were numerically lower with IDeg U200 vs.IGlar (1.22 and 1.42 episodes/patient-year, respectively; estimatedrate ratio (ERR) IDeg/IGlar: 0.86 [95% CI: 0.58; 1.28], p¼0.46). Ratesof nocturnal confirmed hypoglycemia (00:01e05:59 hours) alsowere numerically lower with IDeg (0.18 vs. 0.28 episodes/patient-year, respectively; ERR: 0.64 [95% CI: 0.30; 1.37], p¼0.25). Meandaily basal insulin dose was similar after 26 weeks (IDeg U200, 0.62U/kg; IGlar, 0.66 U/kg). In this trial in insulin-naïve patients withT2D, insulin degludec 200 U/ml improved glycemic control similarto IGlar with a low risk of hypoglycemia.

193

Selective Somatostatin Receptor Type 2 Antagonism PreventsHypoglycaemia In Type 1 Diabetic BB RatsNEGAR KARIMIAN*, TAIRAN QIN, MAYOWA OSUNDIJI, YACHI HUANG,TAO LIANG, MICHAEL RIDDELL, DAVID H. COY, MLADEN VRANIC,HERBERT Y. GAISANOToronto, ON; New Orleans, LA

Impaired counterregulation during hypoglycemia in type 1 dia-betes (T1D) is partly due to inadequate islet alpha-cell glucagonsecretion; this is a limiting factor of intensive insulin treatment.Accentuation of the increased intra-islet somatostatin suppressionof hypoglycemia-stimulated alpha-cell glucagon release during T1Dhas been suggested as one reason. We hypothesized that hypogly-cemia can be prevented in autoimmune T1D by selective somato-statin receptor type 2 (SSTR2) antagonism of alpha cells to relieveSSTR2 inhibition, thereby increasing glucagon secretion. Diabeticbiobreeding diabetes prone (BBDP) rats (D), that mimic humanautoimmune T1D, Vs non-diabetic BBDP(N) rats, underwent 3-hinfusion of vehicle or SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycaemia in vivo, clamped at 3�0.5mmol/l. D rats,treated with SSTR2a, needed 95% less glucose infusion than

untreated D rats (p<0.05) to attain hypoglycaemia, implying thatattenuated glucagon response to hypoglycemia in diabetic BB ratswas restored by SSTR2a. To monitor real-time glucagon secretoryresponse directly, we developed thin slices of pancreas in vitro,subjected to perifusion with vehicle vs SSTR2a, as well as simulta-neous sequential condition changes of non-stimulatory 7mMglucose (G), followed by stimulatory 1mM G and 20mM arginine(7mM G). 30 uM SSTR2a treatment enhanced glucagon secretion inbothNandDBBDP rat slices: 7mMG (by 1-2 fold),1mMG (2-3 fold),and 20mM arginine (in 7mM G, by 2 fold) (p<0.001) compared tovehicle. Thus, somatostatin may contribute to impaired glucagonresponsiveness to hypoglycemia in autoimmune T1D. We concludethat SSTR2 antagonism can enhance hypoglycemia-stimulatedglucagon release sufficient for normoglycemic control.

194

Reduced Risk of Hypoglycemia with Insulin Degludec vs InsulinGlargine in Patients with Type 2 Diabetes Requiring High Dosesof Basal Insulin: Meta-Analysis of Five Randomized TrialsHELENA W. RODBARD, YEHUDA HANDELSMAN, STEPHEN GOUGH,JINA HAHN*, NATHAN LASSOTA, WENDY LANERockville, MD; Tarzana, CA; Oxford, UK; Søborg, Denmark;Asheville, NC

InsulinDegludec (IDeg) is anewbasal insulin thathasanultra-longand flat time-action profile. This study compared IDeg with insulinglargine (IGlar) in patients with type 2 diabetes (T2DM) requiring>60 U/day of basal insulin. This meta-analysis investigated HbA1c,fasting plasma glucose (FPG), and rates of overall confirmed (PG<3.1mmol/L or requiring assistance) and nocturnal (00:01�05:59 hours)confirmed hypoglycemia in a pooled population of T2DM patientsreceiving >60 U of basal insulin at trial completion. Five phase-3a,open-label, randomized, treat-to-target trials with IDeg (n¼2,262)vs. IGlar (n¼1,110) administered once daily by subjects with T2DMwere included. Statistical analysis used ANCOVA (HbA1c and FPG)andnegative binomial regression (rates of hypoglycemia). At end-of-trial, a similar percentage of IDeg- and IGlar-treated T2DM subjectsrequired >60 U of basal insulin daily [IDeg, 35.1% (795/2262); IGlar,33.7% (374/1110)]. Similar glycemic control was obtained for IDeg vsIGlar (HbA1c: 0.05%, NS). End-of-trial FPG values were lower withIDeg than IGlar:�0.33mmol (p¼0.04).Therewas a 21% lower rate ofoverall confirmed hypoglycemic episodes for IDeg (rate ratio (RR)IDeg/IGlar: 0.79, p¼0.02) and a 52% lower rate of nocturnalconfirmed hypoglycemic episodes for IDeg (RR: 0.48, p<0.0001). Inpatients with T2DM requiring >60 U/day of basal insulin, at similarlevels of HbA1c, IDeg achieves significantly lower rates of hypogly-cemiacomparedwith IGlar. Thesefindingsareconsistentwith resultsfor the overall trial population, confirming that IDeg is a safe andeffective basal insulin choice for T2DM patients across the spectrumof insulin requirements.

195

Withdrawn

196

Insulin Degludec Improves Glycemic Control with LowerNocturnal Hypoglycemia Risk than Insulin Glargine: A 2-yearRandomized Trial in Type 1 DiabetesBRUCE W. BODE*, SIMON HELLER, CHARLOTTE T. HANSEN,AZHAR RANA, DAVID L. RUSSELL-JONESAtlanta, GA; Sheffield, UK; Søborg, Denmark; Guildford, UK

This 2-yr, open-label study compared efficacy and safety ofinsulin degludec (IDeg), a new, ultra-long-acting basal insulin, andinsulin glargine (IGlar), in basalebolus (BB) therapy in type 1 dia-betes (T1DM).