Ensor 2015.

Study characteristics
Methods	Study design: parallel randomised controlled trial
Participants	Inclusion criteria: male or female aged between 18 and 75 diagnosed with type 2 diabetes (according to WHO criteria) being treated with diet and exercise alone, and not on any medication for diabetes HbA1c level at screening and baseline greater than 6.6% and less than 9.0% fasting glucose concentration less than 240 mg/dL (13.3 mmol/L) BMI ≤ 45 kg/m² a stable weight (±10%) for 3 months prior to entry into the study Exclusion criteria: treatment with any sulfonylureas, or other antidiabetic medications (e.g. thiazolidinediones, metformin, acarbose, exenatide, or insulin) within the prior 3 months chronic (lasting longer than 14 consecutive days) systemic glucocorticoid treatment within 4 weeks of the baseline visit use of any weight loss drugs within the prior 3 months proliferative retinopathy known or suspected abuse of alcohol or narcotics any experience with hypoglycaemic unconsciousness impaired hepatic, renal, or cardiac function uncontrolled hypertension pregnancy, breastfeeding, or intention of becoming pregnant or judged to be using inadequate contraception documented gastrointestinal disease, or taking of medications to alter gut motility or absorption treatment with any investigational drug within 30 days of the screening visit Diagnostic criteria: "according to WHO criteria" Setting: outpatients Age group: adults Sex: females and males Country where trial was performed: India, USA
Interventions	Intervention(s): Splenda 1.5 g, 3 times a day, dissolved in 125 to 250 mL of water Comparator(s): tagatose 15 g, 3 times a day, dissolved in 125 to 250 mL of water Duration of intervention: 10 months Duration of follow‐up: 10 months Run‐in period: 8 weeks Number of study centres: multicentre study (number of centres not provided)
Outcomes	Reported outcomes in full text of publication: HbA1c, lipid profile (total‐C, HDL, TG), glucose levels (fasting)
Identification	Trial identifier:NCT00955747; CTRI/2009/091/000536 Trial terminated early: no
Publication details	Language of publication: English Funding: commercial funding: Biospherics subsidiary of Spherix Inc; non‐commercial funding: grant from the National Center for Research Resources and the National Center for Advancing Translational Sciences, US National Institutes of Health Publication status: peer‐reviewed journal and full article
Stated aim for study	Quote: "The primary objective of this Phase 3 clinical trial was to evaluate the placebo‐controlled effect of D‐tagatose on glycemic control and safety in subjects with type 2 diabetes over the course of a 10‐month treatment. The secondary objectives of this clinical trial were to evaluate the placebo‐controlled effects of D‐tagatose on fasting blood glucose, insulin, lipid profiles, and changes in BMI."
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote from publication: "A total of 494 subjects were randomized into the study" "There were 494 subjects randomized, 185 subjects in the US and 309 subjects in India", "Randomization was stratified according to screening HbA1c values (<7.5% and ≥7.5%) to achieve a balanced distribution of subjects across two arms (treatment and placebo)" Comment: insufficient information about the sequence generation process
Allocation concealment (selection bias)	Unclear risk	Quote from publication: "This was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel group study" Comment: not clear whether allocation sequence was concealed
Blinding of participants and personnel (performance bias) anthropometric measures other than body weight	Low risk	Quote from publication: "The placebo amounts were chosen to match sweetness for blinding. The powder packets were the same size and bore the same labeling with the exception of the designation 'Substance A' or 'Substance B'" Comment: placebos were described to be similar in sweetness and packaging; investigator‐assessed outcome
Blinding of participants and personnel (performance bias) body weight	Low risk	Quote from publication: "The placebo amounts were chosen to match sweetness for blinding. The powder packets were the same size and bore the same labeling with the exception of the designation 'Substance A' or 'Substance B'" Comment: placebos were described to be similar in sweetness and packaging; investigator‐assessed outcome
Blinding of participants and personnel (performance bias) glucose levels	Low risk	Quote from publication: "The placebo amounts were chosen to match sweetness for blinding. The powder packets were the same size and bore the same labeling with the exception of the designation 'Substance A' or 'Substance B'" Comment: placebos were described to be similar in sweetness and packaging; fasting glucose; investigator‐assessed outcome
Blinding of participants and personnel (performance bias) HbA1c	Low risk	Quote from publication: "The placebo amounts were chosen to match sweetness for blinding. The powder packets were the same size and bore the same labeling with the exception of the designation 'Substance A' or 'Substance B'" Comment: placebos were described to be similar in sweetness and packaging; investigator‐assessed outcome
Blinding of participants and personnel (performance bias) lipid profile	Low risk	Quote from publication: "The placebo amounts were chosen to match sweetness for blinding. The powder packets were the same size and bore the same labeling with the exception of the designation 'Substance A' or 'Substance B'" Comment: placebos were described to be similar in sweetness and packaging; investigator‐assessed outcome
Blinding of outcome assessment (detection bias) anthropometric measures other than body weight	Unclear risk	Comment: the blinding of outcome assessors was not addressed; investigator‐assessed outcome
Blinding of outcome assessment (detection bias) body weight	Unclear risk	Comment: the blinding of outcome assessors was not addressed; investigator‐assessed outcome
Blinding of outcome assessment (detection bias) glucose levels	Low risk	Comment: the outcome is unlikely to have been influenced by lack of blinding; investigator‐assessed outcome
Blinding of outcome assessment (detection bias) HbA1c	Low risk	Comment: the outcome is unlikely to have been influenced by lack of blinding; investigator‐assessed outcome
Blinding of outcome assessment (detection bias) lipid profile	Low risk	Comment: the outcome is unlikely to have been influenced by lack of blinding; investigator‐assessed outcome
Incomplete outcome data (attrition bias) anthropometric measures other than body weight	High risk	Quote from publication: "A total of 494 subjects were randomized into the study (...) Of these, 480 were treated, 248 with placebo and 232 with D‐tagatose" "The ITT population was approximately evenly divided between males and females (...) with approximately equivalent distributions in the D‐tagatose and placebo groups." "Three analysis populations were evaluated: (1) The Intent‐to‐Treat (ITT) population, (2) the Per Protocol (PP) population, and (3) the Safety population." Comment: in total 494 participants were randomised, out of these 356 (72.1%) were analysed in the ITT population, 204 (41.3%) in the PP population, and 392 (79.4%) in the safety population; reasons for attrition were not reported
Incomplete outcome data (attrition bias) body weight	High risk	Quote from publication: "A total of 494 subjects were randomized into the study (...) Of these, 480 were treated, 248 with placebo and 232 with D‐tagatose" "The ITT population was approximately evenly divided between males and females (...) with approximately equivalent distributions in the D‐tagatose and placebo groups." "Three analysis populations were evaluated: (1) The Intent‐to‐Treat (ITT) population, (2) the Per Protocol (PP) population, and (3) the Safety population." Comment: data for body weight (kg) not provided
Incomplete outcome data (attrition bias) glucose levels	High risk	Quote from publication: "A total of 494 subjects were randomized into the study (...) Of these, 480 were treated, 248 with placebo and 232 with D‐tagatose" "The ITT population was approximately evenly divided between males and females (...) with approximately equivalent distributions in the D‐tagatose and placebo groups." "Three analysis populations were evaluated: (1) The Intent‐to‐Treat (ITT) population, (2) the Per Protocol (PP) population, and (3) the Safety population." Comment: in total 494 participants were randomised, out of these 356 (72.1%) were analysed in the ITT population, 204 (41.3%) in the PP population, and 392 (79.4%) in the safety population; reasons for attrition were not reported
Incomplete outcome data (attrition bias) HbA1c	High risk	Quote from publication: "A total of 494 subjects were randomized into the study (...) Of these, 480 were treated, 248 with placebo and 232 with D‐tagatose" "The ITT population was approximately evenly divided between males and females (...) with approximately equivalent distributions in the D‐tagatose and placebo groups." "Three analysis populations were evaluated: (1) The Intent‐to‐Treat (ITT) population, (2) the Per Protocol (PP) population, and (3) the Safety population." Comment: in total 494 participants were randomised, out of these 356 (72.1%) were analysed in the ITT population, 204 (41.3%) in the PP population, and 392 (79.4%) in the safety population; reasons for attrition were not reported
Incomplete outcome data (attrition bias) lipid profile	Unclear risk	Quote from publication: "A total of 494 subjects were randomized into the study (...) Of these, 480 were treated, 248 with placebo and 232 with D‐tagatose" "The ITT population was approximately evenly divided between males and females (...) with approximately equivalent distributions in the D‐tagatose and placebo groups." "Three analysis populations were evaluated: (1) The Intent‐to‐Treat (ITT) population, (2) the Per Protocol (PP) population, and (3) the Safety population." Comment: in total 494 participants were randomised, out of these 356 (72.1%) were analysed in the ITT population, 204 (41.3%) in the PP population, and 392 (79.4%) in the safety population; reasons for attrition were not reported
Selective reporting (reporting bias)	High risk	Comment: body weight and BMI were both measured, but it is only reported that no significant differences were observed between intervention and control groups. For serum insulin concentration, it is only stated that "there was no detectable consistent change in serum insulin concentrations in this trial".
Other bias	Unclear risk	Comment: the study was supported in part by a commercial grant