Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial
Open accessAbstract
Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets. Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss. Design, Setting, and Participants: The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss. Interventions: Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality. Main Outcomes and Measures: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss. Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups. Conclusions and Relevance: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom. Trial Registration: clinicaltrials.gov Identifier: NCT01826591.
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Low-calorie diets typically restrict fats or carbohydrates, and neither is more important for weight loss if only a calorie deficit occurs.
“Low-calorie diets typically restrict fats or carbohydrates, neither of which has been determined to be more important for weight loss if only a calorie deficit occurs.”
From Optimal Diet Strategies for Weight Loss and Weight Loss Maintenance (2021) · cites this paper as [16]
The Conclusions report no significant difference in 12-month weight change between the healthy low-fat and healthy low-carbohydrate diets. The Results report similar reductions in energy intake in both groups, but the Weight Loss Intervention section says participants received no explicit calorie-restriction instructions. The study therefore supports the comparison between diets, not the broader claim that neither matters more whenever a calorie deficit occurs. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAdherence to behavioral therapy sessions is a greater predictor for better outcomes than macronutrient breakdown.
“with adherence to behavioral therapy sessions being a greater predictor for better outcomes than macronutrient breakdown”
From Lifestyle Medicine for Obesity in the Era of Highly Effective Anti-Obesity Treatment (2025) · cites this paper as [182]
The Results report similar attendance in the two diet groups, and the Discussion reports no meaningful difference in weight loss between the low-fat and low-carbohydrate groups (page not available in our copy). The paper does not report that session attendance predicts weight loss, or compare its predictive value with macronutrient breakdown; that is the unsupported part of the claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCalorically restricted low-carbohydrate diets are effective for weight loss.
“Calorically restricted low-carbohydrate diets have been shown to be effective for weight loss”
From Lifestyle Medicine for Obesity in the Era of Highly Effective Anti-Obesity Treatment (2025) · cites this paper as [182]
The Primary Outcome section reports a mean 12-month weight loss of 6.0 kg in the healthy low-carbohydrate group. The Results report that participants reduced their energy intake by approximately 500–600 kcal/day, but the Weight Loss Intervention section explicitly says they were not instructed to restrict calories. The study therefore supports weight loss with a low-carbohydrate diet, but not the characterization of its intervention as prescribed caloric restriction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe DIETFITS study found no significant differences in weight loss between low-fat and low-carbohydrate diets.
“The 2018 the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study found no significant differences in weight loss between low-fat and low-carbohydrate diets.”
From Optimal Diet Strategies for Weight Loss and Weight Loss Maintenance (2021) · cites this paper as [16]
No particular macronutrient breakdown has been shown to be generally superior for weight loss.
“no particular macronutrient breakdown has been shown to be generally superior for weight loss”
From Lifestyle Medicine for Obesity in the Era of Highly Effective Anti-Obesity Treatment (2025) · cites this paper as [182]
Overweight and obesity are increasingly prevalent in people with type 1 diabetes and present clinical challenges regarding diabetes treatment and CVD risk factors.
“Overweight and obesity are also increasingly prevalent in people with type 1 diabetes and present clinical challenges regarding diabetes treatment and CVD risk factors (133,134).”
From Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report (2019) · cites this paper as [133]
The paper’s Weight Loss Intervention and Outcome Measurements sections describe a diet trial in overweight adults, including measurements of weight and metabolic risk factors (page unavailable in our copy). Searches for type 1 diabetes, increasing obesity prevalence in that population, and related treatment or CVD challenges found no passage addressing the claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn that 12-month intervention, both low-carbohydrate and low-fat groups showed reductions in fasting glucose, insulin, and triglycerides, with no statistically significant differences between interventions; low-carbohydrate was also associated with increased HDL cholesterol and a modest increase in LDL cholesterol.
“Both groups showed reductions in fasting glucose, insulin, and triglycerides, with no statistically significant differences between interventions. LC was also associated with increased HDL cholesterol and a modest increase in LDL cholesterol [45].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [45]
In a 12-month intervention without a centrally imposed energy deficit, low-carbohydrate and low-fat diets produced comparable reductions in body weight (6.0 kg and 5.3 kg respectively), accompanied by substantial individual variability ranging from weight losses up to 25 kg to weight gain in some participants.
“In a 12-months intervention without a centrally imposed energy deficit, LC and LF produced comparable reductions in body weight (6.0 kg and 5.3 kg respectively), accompanied by substantial individual variability, ranging from weight losses of up to 25 kg to weight gain in some participants [45].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [45]
Compared with lean individuals, those with obesity demonstrated lower postprandial responses of peptide YY and GLP-1 both before and after weight reduction.
“Compared with lean individuals, those with obesity demonstrated lower postprandial responses of peptide YY and GLP 1 both before and after weight reduction [45].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [45]
In the 12-month study, individual weight changes in the LC and LF groups ranged widely, from significant weight loss to weight gain, despite comparable mean results for the studied groups.
“In the 12-month study, individual weight changes in the LC and LF groups ranged widely, from significant weight loss to weight gain, despite comparable mean results for the studied groups, highlighting the wide variability in response to these strategies [45].”
From Dietary and Behavioral Strategies for Weight Loss and Weight Loss Maintenance: A Narrative Review (2025) · cites this paper as [45]
In the DIETFITS trial, no significant diet-genotype interaction or diet-insulin interaction was observed.
“Additionally, no significant diet–genotype interaction (p = 0.20) or diet–insulin interaction (p = 0.47) was observed.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [92]
In the DIETFITS trial, secondary outcomes favored the healthy low-fat diet for LDL and the healthy low-carbohydrate diet for HDL and triglycerides.
“Secondary outcomes favored HLF for low-density lipoprotein (−5.74 mg/dL; 95% CI, −9.38 to −2.09) and HLC for high-density lipoprotein cholesterol (2.24 mg/dL; 95% CI, −3.33 to −1.15) and triglycerides (−18.25 mg/dL; 95% CI, −28.84 to −7.65) [92].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [92]
Recent precision-based trials underscore the efficacy of personalized weight loss interventions.
“Recent precision-based trials underscore the efficacy of personalized weight loss interventions, providing promising data for future, individualized approaches.”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [92]
In the DIETFITS trial, there was no significant difference in weight change between the healthy low-fat and healthy low-carbohydrate groups at 12 months.
“The results showed no significant difference in weight change between the HLF (−5.3 kg) and HLC (−6.0 kg) groups (mean difference 0.7 kg; 95% CI, −0.2 to 1.6; p = 0.20).”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [92]
In DIETFITS, weight loss was greater when consuming a low-carbohydrate than low-fat diet at 3 and 6 months, a difference that did not persist at 12 months.
“In DIETFITS (Diet Intervention Examining The Factors Interacting with Treatment Success), weight loss was greater when consuming a low-carbohydrate than when consuming a low-fat diet at 3 and 6 mo, a difference that did not persist at 12 mo (156, 157).”
From The carbohydrate-insulin model: A physiological perspective on the obesity pandemic (2021) · cites this paper as [156]
Previous studies have focused on comparing low-carbohydrate to low-fat eating patterns.
“Instead, previous studies have focused on comparing low-carb to low-fat eating patterns (3–10).”
Low-carbohydrate patterns generally refer to patterns with total carbohydrate targets between 20% and 40% of kilocalories.
“Low-carbohydrate patterns generally refer to patterns with total carbohydrate targets between 20% and 40% of kilocalaroies.20,[29][30][31][32][33][34][35][36]”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [35]
Low-fat patterns generally target total fat intake between 20% and 30% of kilocalories alongside other healthy dietary guidelines.
“Low-fat patterns generally target total fat intake between 20% and 30% of kilocalories alongside other healthy dietary guidelines.20,[29][30][31][32][33][34][35][36]”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [35]
For those following low-carbohydrate diets, meats and animal-sourced foods tend to be overemphasized, leading to inappropriate restriction of fiber and increased saturated fat intake.
“For those following lowcarbohydrate diets, meats and animal-sourced foods tend to be overemphasized, leading to inappropriate restriction of fiber and increased saturated fat intake.29,35,36,42,43”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [35]
A healthy low-carbohydrate diet has been shown to beneficially influence weight loss and cardiometabolic risk factors equivalently to a healthy low-fat pattern.
“In addition, a healthy low-carbohydrate diet has been shown to beneficially influence weight loss and cardiometabolic risk factors equivalently to a healthy low-fat pattern.35”
From Popular dietary patterns: alignment with American Heart Association 2021 dietary guidance: a scientific statement from the American Heart Association. (2023) · cites this paper as [35]
Both groups in the DIETFITS Trial lost a similar amount of weight at 12 months despite substantial differences in the balance of fat and carbohydrate intake.
“Both groups lost a similar amount of weight at 12 months despite substantial differences in the balance of fat and carbohydrate intake.”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [54]
The 2018 DIETFITS Trial concluded that baseline insulin-30 was not a significant effect modifier of weight loss for those randomized to a healthy low-carbohydrate versus a healthy low-fat diet.
“Yet the 2018 DIETFITS Trial, which included more than 600 participants, concluded that baseline insulin-30 (insulin level 30 minutes into an oral glucose tolerance test, a proxy used for insulin resistance) was not a significant effect modifier of weight loss for those randomized to a healthy low-carbohydrate vs. a healthy a low-fat diet [54].”
From Benefits of low carbohydrate diets: a settled question or still controversial? (2021) · cites this paper as [54]
No single eating plan approach has been proven to be consistently superior for weight loss in people with diabetes.
“However, no single approach has been proven to be consistently superior (70,(123)(124)(125), and more data are needed to identify and validate those meal plans that are optimal with respect to long-term outcomes and acceptability.”
From 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes:<i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [124]
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Self-citation
- Authors
- Gardner, C. D., Trepanowski, J. F., Del Gobbo, L. C., Hauser, M. E., Rigdon, J., Ioannidis, J. P. A., Desai, M., & King, A. C.
- Affiliations
- Stanford Medicine (US)
- Stanford Prevention Research Center, Department of Medicine, Stanford University Medical School, Stanford, California
- Corresponding author
- Gardner, Christopher D.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2018-02-20
- Volume
- 319
- Issue
- 7
- Pages
- 667
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5839290
- OpenAlex
- W2790416311
- Cited by
- 709
- References
- 46
- Citations by year
- 2026: 52 · 2025: 66 · 2024: 70 · 2023: 62 · 2022: 91 · 2021: 85 · 2020: 138 · 2019: 84 · 2018: 59
- FWCI
- 62.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k12gm088033-05)
- National Heart, Lung, and Blood Institute (T32HL007034)
- National Institute of General Medical Sciences (K12-GM088033)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK091831, P30DK116074)
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- low-fat diet, low-carbohydrate diet, weight loss, overweight adults, single nucleotide polymorphisms, insulin secretion, macronutrient distribution, personalized nutrition, behaviour change interventions, fasting blood glucose, HOMA-IR
- MeSH terms
- Adult, Energy Intake, Diet, Reducing, Female, Genotype, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Obesity, Weight Loss, Diet, Fat-Restricted, Overweight, Diet, Carbohydrate-Restricted, Young Adult
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