Effect and Safety of Liraglutide 3.0 mg in Subjects With Overweight or Obesity and Type 2 Diabetes Mellitus Treated With Basal Insulin

Phase 3

Completed

• Conditions: Metabolism and Nutrition Disorder; Obesity
• Interventions: Drug: Placebo; Drug: Liraglutide 3.0 mg

• Registration Number: NCT02963922
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This trial is conducted globally. The aim of this trial is to investigate effect and safety of liraglutide 3.0 mg in subjects with overweight or obesity and type 2 diabetes mellitus treated with basal insulin.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-11-10
• Study First Submitted QC: 2016-11-10
• Study First Posted: 2016-11-15
• Study Start: 2017-02-06
• Primary Completion: 2018-09-10
• Study Completion: 2018-09-25
• Results First Submitted: 2019-09-04
• Results First Submitted QC: 2019-11-08
• Results First Posted: 2019-11-27
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-13
• Last Update Posted: 2020-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 396

Inclusion Criteria

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Diagnosed with type 2 diabetes mellitus - Treatment with up to 2 OADs (oral anti-diabetic) (metformin, glitazone, SGLT-2 inhibitor (sodium-glucose cotransporter-2 inhibitors) or sulphonylurea) - Stable treatment with basal insulin according to its label (no requirement of minimum or maximum dose) for at least 90 days prior to screening, as judged by the investigator - HbA1c (glycosylated haemoglobin) 6.0-10.0% (both inclusive) - BMI (body mass index) equal to or above 27 kg/m^2 - Age at least 18 years at the time of signing informed consent

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Exclusion Criteria

• Diagnosis of type 1 diabetes - Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8 (see Section 8.2.3) - Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator - Unable or unwilling to perform self-monitoring of plasma glucose according to the protocol and to keep a diabetes diary - Treatment with any hypoglycaemic medications other than OADs and basal insulin within the past 90 days prior to screening - Treatment with a DPP-IV (dipeptidyl peptidase-4) inhibitor within the past 90 days prior to screening - Recent history of cardiovascular disease (myocardial infarction or stroke within the past 6 months), severe congestive heart failure (NYHA class III, IV), or second degree or greater heart block - Personal or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN2) - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice) - For Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner - Use in past 90 days of medications known to induce significant weight loss (e.g., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics) - History of pancreatitis (acute or chronic) - History of major depressive disorder within the past 2 years - Any lifetime history of a suicide attempt - Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic above or equal to 180 mmHg or diastolic above or equal to110 mmHg). - History of malignancy (except for non-melanoma skin cancer) within the past 5 years

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
liraglutide 3.0 mg	Liraglutide 3.0 mg	-

Primary Outcome Measures

Name	Time	Method
Participants Losing at Least 5% of Baseline Body Weight	Week 56	The estimated percentage of participants losing at least 5% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events \[AEs\]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Change in Body Weight (%)	Week 0, week 56	Change in body weight from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events \[AEs\]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

Secondary Outcome Measures

Name	Time	Method
Change in Waist Circumference	Week 0, week 56	Change in waist circumference from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Responder Definition Value for IWQoL-Lite for CT Physical Function Domain Score	Week 56	Percentage of participants who achieve responder definition value for IWQoL-Lite for CT physical function domain score was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in FPG	Week 0, week 56	Change in fasting plasma glucose (FPG) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Change in Total Daily Basal Insulin Dose (U/kg)	Week 0, week 56	Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Total Daily Insulin Dose (U/kg)	Week 0, week 56	Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in 7-point SMPG Profile Mean Daytime Glucose Value	Week 0, week 56	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner and at bedtime. Change from baseline (week 0) to week 56 in 7-point self-measured plasma glucose (SMPG) profile mean daytime glucose value was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in sBP and dBP	Week 0, week 56	Change in systolic blood pressure (sBP) and diastolic blood pressure (dBP) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Lipids -Total Cholesterol, HDL, LDL, VLDL, Triglycerides and FFA	Week 0, week 56	Change in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids (FFA) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in SF-36: Sub-domains	Week 0, week 56	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in the sub-domain scores was presented based on in-trial data. A positive change score indicates an improvement since baseline. Results are presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Participants Losing More Than 10% of Baseline Body Weight at Week 56	Week 56	The estimated percentage of participants losing more than 10% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events \[AEs\]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Change in HbA1c	Week 0, week 56	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score	Week 0, week 56	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) in SF-36 physical functioning score was presented based on in-trial data and on-drug data. A positive change score indicates an improvement since baseline.
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT), Physical Function Domain (5-items) Score	Week 0, week 56	Change in IWQoL-Lite for CT physical function domain (5-items) score. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. The endpoint was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Change in Total Daily Insulin Dose (U)	Week 0, week 56	Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Total Daily Basal Insulin Dose (% of Pre-trial Dose in U)	Week 0, week 56	Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in SF-36: Physical Component Summary (PCS)	Week 0, week 56	Change in short form 36 v2.0 acute domain physical component summary (PCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The physical component summary (PCS) measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.
Change in SF-36: Mental Component Summary (MCS)	Week 0, week 56	Change in short form 36 v2.0 acute domain mental component summary (MCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The mental component summary (MCS) measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.
Change in IWQoL-Lite for CT: Pain/Discomfort Domain Score	Week 0, week 56	Change in IWQoL-Lite for CT pain and discomfort domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in IWQoL-Lite for CT: Psychosocial Domain Score	Week 0, week 56	Change in IWQoL-Lite for CT psychosocial domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in IWQoL-Lite for CT: Total Score	Week 0, week 56	Change in IWQoL-Lite for CT total score from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Weight Related Sign and Symptom (WRSS) Measure, Categorical Responses	Week 0, week 56	The WRSS measure is a questionnaire under development. The version applied in this study has 10 items that measure the presence and bothersomeness of 10 weight-related symptoms. Each item has a categorical part with answers on the following 5 possible levels: 'Never/Almost never', 'Rarely', 'Sometimes', 'Often' and 'Almost always/Always'. Number of participants in each category at baseline (week 0) and week 56 was presented. Scoring algorithm was not available prior to database lock and therefore it was decided and documented in the statistical analysis plan that WRSS total score was not to be calculated and analyzed.
Participants Who Achieved (Yes/no): HbA1c <7% and Weight Loss ≥5%	Week 56	Percentage of participants who achieved HbA1c \<7% and weight loss ≥5% from baseline at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Participants Who Achieved (Yes/no): HbA1c <7%, Weight Loss ≥5% and no Documented Symptomatic Hypoglycaemia	Week 56	Percentage of participants who achieved HbA1c \<7%, weight loss ≥5% from baseline and no documented symptomatic hypoglycaemia at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Participants Who Achieved (Yes/no): ≥4.3 T-score Points Increase From Baseline in SF-36 Acute Physical Functioning Score	Week 56	Percentage of participants who achieved ≥4.3 T-score points increase from baseline in SF-36 acute physical functioning score at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Participants Who Achieved (Yes/no): ≥3.8 T-score Points Increase From Baseline in SF-36 Acute PCS	Week 56	Percentage of participants who achieved ≥3.8 T-score points increase from baseline in SF-36 acute PCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Participants Who Achieved (Yes/no): ≥4.6 T-score Points Increase From Baseline in SF-36 Acute MCS	Week 56	Percentage of participants who achieved ≥4.6 T-score points increase from baseline in SF-36 acute MCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Adverse Events (AEs)	Week 0 to week 56 + 30 days	An AE was defined as any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. Number of AEs from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on in-trial data was presented. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Number of Hypoglycaemic Episodes	Week 0 to week 56 + 30 days	Number of hypoglycaemic episodes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Physical Examination	Week -1, week 56	Physical examination parameters are categorised as abdomen; gastrointestinal system; cardiovascular system; central and peripheral nervous system; general appearance; head, eyes, ears, nose, throat (ENT) and neck; lymph node palpation; musculoskeletal system; respiratory system; skin and thyroid gland. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -1) and week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Resting Pulse	Week -1, week 56	Change from baseline (week -1) to week 56 in resting pulse was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Electrocardiogram (ECG)	Week -1, week 56	The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 56 were presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Measurements (Haematology) - Haemoglobin	Week 0, week 56	Change from baseline (week 0) to week 56 in haemoglobin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Measurements (Haematology) - Haematocrit	Week 0, week 56	Change from baseline (week 0) to week 56 in Haematocrit was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Measurements (Haematology) - Erythrocytes	Week 0, week 56	Change from baseline (week 0) to week 56 in erythrocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Measurements (Haematology) - Thrombocytes, Leukocytes	Week 0, week 56	Change from baseline (week 0) to week 56 in thrombocytes and leukocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Albumin	Week 0, week 56	Change from baseline (week 0) to week 56 in albumin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase	Week 0, week 56	Change from baseline (week 0) to week 56 in alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Bicarbonate, Total Calcium, Potassium, Sodium and Urea	Week 0, week 56	Change from baseline (week 0) to week 56 in bicarbonate, total calcium, potassium, sodium and urea was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Total Bilirubin and Creatinine	Week 0, week 56	Change from baseline (week 0) to week 56 in total bilirubin and creatinine was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - High Sensitive C-reactive Protein	Week 0, week 56	Change from baseline (week 0) to week 56 in high sensitive C-reactive protein was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - eGFR	Week 0, week 56	Change from baseline (week 0) to week 56 in estimated GFR serum using Modification of Diet in Renal Disease (MDRD) formula was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Uric Acid	Week 0, week 56	Change from baseline (week 0) to week 56 in uric acid was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Calcitonin	Week 0, week 56	Change from baseline (week 0) to week 56 in calcitonin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Change in Laboratory Parameters (Biochemistry) - Thyroid Stimulating Hormone	Week 0, week 56	Change from baseline (week 0) to week 56 in thyroid stimulating hormone was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

Trial Locations

Locations (1)

Novo Nordisk Investigational Site; 🇹🇷 Izmir, Turkey