Table 1.

Overview of study hypotheses and research questions.

Measures		Outcomes	Timeframe	Hypothesis or question
Primary outcome
	Bodyweight scale	Change in body mass (in kilograms)	12 weeks	Those in the Keyto intervention arm will achieve greater weight loss at 12 weeks than those in the Weight Watchers arm.
Secondary outcome
	Bodyweight scale
		Change in body mass (in kilograms)	24 and 48 weeks	Those in the Keyto intervention arm will achieve greater weight loss at 24 and 48 weeks than those in the Weight Watchers arm.
		Change in body mass (in kilograms)	Daily weight measured during the first 12 weeks	What are the patterns of body mass change during the first 12 weeks between the 2 study groups?
	Automated self-administered 24-hour dietary recall
		Carbohydrate intake in 24-hour period (in grams)	12, 24, and 48 weeks	Those in the Keyto intervention arm will report lower carbohydrate intake at 12, 24, and 48 weeks.
		Total fat, saturated fat, polyunsaturated fat, monounsaturated fat intake in 24-hour period (in grams)	12, 24, and 48 weeks	Does the Keyto intervention or WW app intervention influence fat intake from baseline to 12, 24, and 48 weeks?
		Total energy intake in 24-hour period (in kilocalories)	12, 24, and 48 weeks	We will examine changes from baseline to 12, 24, and 48 weeks in total energy intake in the Keyto and Weight Watchers groups.
	Venous blood sample	HbA1ca, fasting glucose, fasting insulin, fasting high-sensitivity C-reactive protein, fasting HOMA-IRb, fasting total cholesterol, fasting HDLc cholesterol, fasting lipoprotein fractions, fasting lipoprotein (a), fasting triglycerides, fasting non-HDL cholesterol	12 and 48 weeks	We will examine changes from baseline to 12 and 48 weeks in metabolic and cardiovascular risk blood biomarkers in the Keyto and Weight Watchers groups.
Exploratory outcome
	Venous blood sample	Fasting albumin, fasting globulin, fasting total bilirubin, fasting alkaline phosphatase, fasting aspartate aminotransferase, fasting alanine aminotransferase	12 and 48 weeks	We will explore changes from baseline to 12 and 48 weeks in blood biochemistry in the Keyto and Weight Watchers group.
Manipulation checks
	Questionnaires
		Food attitude survey	12, 24, and 48 weeks	We will examine all baseline questionnaires as potential covariates. We will also examine differences in questionnaire measures between the 2 groups at 12, 24, and 48 weeks.
		Cravings, mood, and energy	Weekly
		Self-reported dietary adherence	Weekly
		Pittsburgh Sleep Quality Index	12, 24, and 48 weeks

^aHbA₁c: hemoglobin A₁c.

^bHOMA-IR: homeostasis model assessment of insulin resistance.

^cHDL: high-density lipoprotein.