Relationship between A1C and Hypoglycemia Risk in Individual Patients Comparing Insulin Degludec with Insulin Glargine U100
Authors: PHILIS-TSIMIKAS ATHENA , LANE WENDY , PEDERSEN-BJERGAARD ULRIK , WYSHAM CAROL H. , BARDTRUM LARS , ØSTOFT SIGNE H. , HELLER SIMON 
Published: June 2018

Targeting a lower A1C may increase the hypoglycemia risk in patients with diabetes. To investigate the relationship between A1C and hypoglycemia risk on an individual level, this post-hoc analysis used data from two double-blind, randomized, treat-to-target, two-period (32 weeks each) crossover trials of insulin degludec (degludec) vs. insulin glargine 100 units/mL (glargine U100) in patients with type 1 (T1D; SWITCH 1, n=501) or type 2 diabetes (T2D; SWITCH 2, n=721). For each patient at each visit, A1C was linked with the number of hypoglycemic events (blood glucose-confirmed [&lt;56 mg/dL] with symptoms or severe [third-party assistance]) since last visit. A 1% (10.9 mmol/mol) A1C reduction led to an 18% (degludec) and 34% (glargine U100) increased risk of hypoglycemia in T1D, and 45% (degludec) and 67% (glargine U100) increased risk in T2D (Fig). Assuming an 11% (T1D) and 30% (T2D) reduction in hypoglycemia risk, as seen in the SWITCH trials, this can be translated into a 0.61% (T1D) and 0.67% (T2D) A1C reduction with degludec with no increase in hypoglycemia risk vs. glargine U100.
In conclusion, lowering A1C led to a higher hypoglycemia risk; however, the lower incremental hypoglycemia risk with degludec vs. glargine U100 may allow for a lower A1C target in both T1D and T2D with degludec than with glargine U100 in clinical practice, when hypoglycemia is a limiting factor for glycemic control.

Disclosure
A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca. W. Lane: Advisory Panel; Self; Novo Nordisk A/S, Insulet Corporation, Intarcia Therapeutics, Inc., Sanofi. Research Support; Self; Novo Nordisk A/S, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Sanofi, Dexcom, Inc.. Speaker's Bureau; Self; Novo Nordisk A/S, Insulet Corporation. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Consultant; Self; Medtronic. C.H. Wysham: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Insulet Corporation, Novo Nordisk Inc., Sanofi. L. Bardtrum: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. S.H. Østoft: Employee; Self; Novo Nordisk A/S. S. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Takeda, Sanofi-Aventis, Boehringer Ingelheim GmbH. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company, Merck Sharp & Dohme Corp., Takeda, AstraZeneca, Boehringer Ingelheim GmbH.