Victoza

After a week of habituation, the standard rat chow (SRC, catalog number: CE-2, CLEA
Japan, Inc., Tokyo, Japan) was changed to a fructose-rich diet (FRD, 60% fructose purified
diet, catalog number: 5375, PMI Nutrition International, St. Louis, MO, U.S.A.) at 6 weeks
of age. WBKDF rats (n=24) at 7 weeks of age were randomly divided into three groups of
eight rats each: a control group, a low dose (75 µg/kg) of liraglutide
group and a high dose (300 µg/kg) of liraglutide group. The doses of
liraglutide were selected based on results from previous studies [26 (link), 27 (link)]. Saline or liraglutide
(Victoza^®, purchased from Novo Nordisk Pharma Ltd., Tokyo, Japan) was
administered subcutaneously once daily for 4 weeks. The body weight of the rats was
measured weekly between 10:00 and 14:00 hr. Non-fasting plasma glucose levels were
measured weekly using blood samples collected from the tail vein. Age-matched WBKDF rats
fed the SRC (n=8) were used as intact controls for measurement of blood pressure and
histopathological examination of the liver.

The study was a 12‐week, multicenter, open‐label, prospective, randomized, parallel‐group comparison trial that was carried out at six medical institutions (Hokkaido University Hospital, Tomakomai City Hospital, Kushiro Red Cross Hospital, Manda Memorial Hospital, Kurihara Clinic and Aoki Clinic). Participants were Japanese patients with type 2 diabetes being treated at these centers. After obtaining informed consent from the patients, they were randomly assigned to either continue taking liraglutide (Victoza^®; Novo Nordisk Pharma, Copenhagen, Denmark) once daily before breakfast (Lira group) or switch to weekly administration of dulaglutide (Trulicity^®; Eli Lilly, Indianapolis, IN, USA and Sumitomo Dainippon Pharma Co., Ltd, Osaka, Japan; Dula group). Randomization of patients and allocation to each treatment group were carried out using a central computer‐based randomization system. Patients were stratified by screening age (<65 or ≥65 years), HbA1c (<7.5 or ≥7.5%) and body mass index (<25 or ≥25 kg/m²).

After a 2‐week screening, eligible patients were randomized 1:1:1 to receive either subcutaneous liraglutide (Victoza; Novo Nordisk, Bagsvaerd, Denmark) 1.8 mg once daily, oral sitagliptin (Januvia; Merck & Co., Inc., Kenilworth, NJ) 100 mg once daily, or subcutaneous insulin glargine (Lantus; Sanofi, Bridgewater, NJ) at bedtime plus metformin (Glucophage; Bristol‐Myers Squibb Company, NJ) for 26 weeks (Fig. 1).
A randomization list was generated using Statistical Analysis System (SAS Institute, Inc., Cary, NC), and patients were allocated using a secure Oracle‐based interactive web response system (Jiaxing Taimei Medical Technology, Shanghai, China) in accordance with the sequence from the randomization list. After appropriate titrations, all dosages were sustained during the treatment period. All patients received diabetes education, which was routine clinical practice, including dietary and exercise suggestions according to China guidelines16 at enrollment, with reinforcement throughout the study.
Liraglutide was initiated at 0.6 mg/day and then increased by weekly forced titration to 1.8 mg/day or the maximum tolerated dose (at least 1.2 mg/day). Insulin glargine was started at 0.2 IU/kg/day and was then titrated by 2 to 6 units each day to achieve fasting plasma glucose (FPG) <7 mmol/L. Metformin was administered at a constant dose.