Phase 3
Completed N=302
Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus
Source: ClinicalTrials.gov NCT03086330 ↗Enrolled (actual)
302
Serious AEs
4.3%
Results posted
Aug 2019
Primary outcomePrimary: Change in HbA1c — -1.6; -0.2 Percentage of HbA1c — p=<0.0001
◆ Published Evidence
Highly cited
364citations · ~52 / year
Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial.
Summary
This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo as add-on to sodium glucose co-transporter-2 inhibitor (SGLT-2i) monotherapy or in combination with either metformin or sulfonylurea on glycaemic control after 30 weeks of treatment in subjects with type 2 diabetes. Subjects will remain on their pre-trial medication.
Linked Publications
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Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in HbA1c |
-1.6; -0.2 | <0.0001 sig |
| SECONDARY Change in Body Weight (kg) |
-4.7; -1.0 | <0.0001 sig |
| SECONDARY Change in Fasting Plasma Glucose (FPG) |
-2.26; 0.07 | — |
| SECONDARY Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean 7-point Profile |
-2.6; -0.3 | — |
| SECONDARY Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean Post Prandial Increment (Over All Meals) |
-1.2; 0.0 | — |
| SECONDARY Change in Fasting Blood Lipid, Total Cholesterol |
0.91; 1.02 | — |
| SECONDARY Change in Fasting Blood Lipid, Low-density Lipoprotein (LDL) Cholesterol |
0.90; 1.04 | — |
| SECONDARY Change in Fasting Blood Lipid, High-density Lipoprotein (HDL) Cholesterol |
0.99; 1.01 | — |
| SECONDARY Change in Fasting Blood Lipid, Triglycerides |
0.81; 0.97 | — |
| SECONDARY Change in Body Weight (%) |
-5.4; -1.0 | — |
| SECONDARY Change in Body Mass Index |
-1.7; -0.4 | — |
| SECONDARY Change in Waist Circumference |
-4.4; -1.8 | — |
| SECONDARY Change in Systolic Blood Pressure |
-4.3; 1.1 | — |
| SECONDARY Change in Diastolic Blood Pressure |
-0.1; -0.1 | — |
| SECONDARY Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains |
1.9; 0.7; 1.3; 1.1; 1.5; 0.0 | — |
| SECONDARY Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately |
-2.2; -0.8; 0.3; -0.4; 4.2; 1.9 | — |
| SECONDARY HbA1c Below 7.0% (53 mmol/Mol) |
82.5; 20.5 | — |
| SECONDARY HbA1c Equal to or Below 6.5% (48 mmol/Mol) |
60.0; 3.9 | — |
| SECONDARY Weight Loss Equal to or Above 3% |
69.4; 21.1 | — |
| SECONDARY Weight Loss Equal to or Above 5% |
50.4; 7.8 | — |
| SECONDARY Weight Loss Equal to or Above 10% |
15.7; 1.6 | — |
| SECONDARY HbA1c Below 7.0% (53 mmol/Mol) Without Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain |
72.5; 17.3 | — |
| SECONDARY HbA1c Reduction Equal to or Above 1%-Point |
80.8; 15.0 | — |
| SECONDARY HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 3% |
56.7; 7.9 | — |
| SECONDARY HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 5% |
41.7; 4.7 | — |
| SECONDARY HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 10% |
15.0; 1.6 | — |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAEs) |
356; 247 | — |
| SECONDARY Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes |
4; 0 | — |
| SECONDARY Change in Haematology: Haemoglobin |
1.1; 1.1 | — |
| SECONDARY Change in Haematology: Haematocrit |
1.4; 1.1 | — |
| SECONDARY Change in Haematology: Thrombocytes |
25.3; 20.2 | — |
| SECONDARY Change in Haematology: Erythrocytes |
0.16; 0.11 | — |
| SECONDARY Change in Haematology: Leucocytes |
0.65; 0.54 | — |
| SECONDARY Change in Biochemistry: Amylase |
10.2; 5.0 | — |
| SECONDARY Change in Biochemistry: Lipase |
11.6; 4.5 | — |
| SECONDARY Change in Biochemistry: Alkaline Phosphatase |
4.6; 7.2 | — |
| SECONDARY Change in Biochemistry: Alanine Aminotransferase |
4.5; 4.8 | — |
| SECONDARY Change in Biochemistry: Aspartate Aminotransferase |
3.4; 3.5 | — |
| SECONDARY Change in Biochemistry: Total Bilirubin |
2.3; 1.7 | — |
| SECONDARY Change in Biochemistry: Albumin |
0.1; 0.1 | — |
| SECONDARY Change in Biochemistry: Calcium (Total) |
0.04; 0.05 | — |
| SECONDARY Change in Biochemistry: Potassium |
0.3; 0.2 | — |
| SECONDARY Change in Biochemistry: Sodium |
1.7; 1.5 | — |
| SECONDARY Change in Biochemistry: Bicarbonate |
2.2; 2.1 | — |
| SECONDARY Change in Biochemistry: Estimated Glomerular Filtration Rate (eGFR) |
3.4; 3.2 | — |
| SECONDARY Change in Biochemistry: Creatinine |
4.6; 2.6 | — |
| SECONDARY Change in Calcitonin |
1.3; 1.7 | — |
| SECONDARY Change in Pulse |
4.0; 0.1 | — |
| SECONDARY Change in Electrocardiogram |
62.4; 66.2; 36.9; 32.5; 0.7; 1.3 | — |
| SECONDARY Change in Physical Examination: General Appearance |
90.0; 86.0; 10.0; 14.0; 0; 0 | — |
| SECONDARY Change in Physical Examination: Central and Peripheral Nervous System |
92.0; 86.7; 7.3; 12.7; 0.7; 0.7 | — |
| SECONDARY Change in Physical Examination: Cardiovascular System |
98.7; 93.3; 1.3; 6.0; 0; 0.7 | — |
| SECONDARY Change in Physical Examination: Gastrointestinal System Including Mouth |
93.3; 93.3; 6.7; 6.7; 0; 0 | — |
| SECONDARY Change in Physical Examination: Skin |
91.3; 93.3; 8.7; 6.7; 0; 0 | — |
| SECONDARY Change in Physical Examination: Respiratory System |
100; 98.7; 0; 1.3; 0; 0 | — |
| SECONDARY Change in Physical Examination: Lymph Node Palpation |
99.3; 100; 0.7; 0; 0; 0 | — |
| SECONDARY Change in Physical Examination: Thyroid Gland |
98.0; 96.7; 2.0; 3.3; 0; 0 | — |
| SECONDARY Change in Fundoscopy |
70.7; 62.0; 24.7; 32.7; 4.7; 5.3 | — |
Eligibility Criteria
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
- Male or female, above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age equal to or above 20 years at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus
- HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
- Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (equal to or above 1500 mg or maximum tolerated dose) or a SU for at least 90 days prior to the day of screening. All medications in compliance with current local label
Exclusion Criteria
- 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)
- Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed
- Subjects with alanine aminotransferase above 2.5 x upper normal limit
- Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative
- History or presence of pancreatitis (acute or chronic)
- History of diabetic ketoacidosis
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
- Subjects presently classified as being in New York Heart Association Class IV
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Renal impairment measured as estimated Glomerular Filtration Rate value of eGFR below 60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry for serum creatinine measured at screening
- Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within the past 90 days prior to randomisation
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed
Data sourced from ClinicalTrials.gov (NCT03086330) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.