Prediabetes syndrome

Summary

Prediabetes syndrome (MONDO:0006920) is a disease with 14 GWAS associations across 2 studies and 630 clinical trials. Top therapeutic interventions include berberine, saxagliptin anhydrous, and bromocriptine. A subtype of glucose metabolism disease — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• GWAS associations: 14
• Clinical trials: 630

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	prediabetes syndrome
Mondo ID	MONDO:0006920
EFO	EFO:1001121
MeSH	D011236
DOID	DOID:11716
ICD-11	1583355636
NCIT	C122685
UMLS	C0362046
MedGen	83928
MedDRA	10065542
Is cancer (heuristic)	no

Also known as: borderline diabetes · prediabetes

Data availability: 14 GWAS associations (2 studies).

Disease family

This is a subtype of glucose metabolism disease. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › glucose metabolism disease › prediabetes syndrome

Related subtypes (8): glucose intolerance, hyperinsulinism, hyperglycemia, hypoglycemia, diabetes mellitus, triosephosphate isomerase deficiency, disorder of gluconeogenesis, glyceraldehyde-3-phosphate dehydrogenase deficiency

Genetics & variants

GWAS landscape

14 GWAS associations across 2 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2908293	8e-09	GCK	A	1.25
rs2300584	1e-08	GCK	G	1.25
rs10259649	1e-08	GCK	C	1.25
rs72805692	2e-08	HK1	A	1.46
rs17476364	2e-08	HK1	T	1.45
rs2971671	4e-08	GCK	C	1.23
rs2908292	4e-08	GCK	T	1.23

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90502762	Aliyu U	2025	2,267	8,665	Genetic risk and polygenic risk score assessment of prediabetes and progression to type 2 diabetes.
GCST90502763	Aliyu U	2025	2,267	8,665	Genetic risk and polygenic risk score assessment of prediabetes and progression to type 2 diabetes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	7
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	7

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2908293	7	44169723	G>A,C	0.25	intron_variant	GCK	8e-09	Tier 4: intronic/intergenic
rs2300584	7	44179739	A>G,T	0.25	intron_variant	GCK	1e-08	Tier 4: intronic/intergenic
rs10259649	7	44180106	T>C	0.25	intron_variant	GCK	1e-08	Tier 4: intronic/intergenic
rs72805692	10	69339353	A>G	0.07	intron_variant	HK1	2e-08	Tier 4: intronic/intergenic
rs17476364	10	69334748	T>C	0.07	intron_variant	HK1	2e-08	Tier 4: intronic/intergenic
rs2971671	7	44171738	T>C	0.28	intron_variant	GCK	4e-08	Tier 4: intronic/intergenic
rs2908292	7	44171111	C>G,T	0.28	intron_variant	GCK	4e-08	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alcohol	Phase 3 (in late-stage trials)
Insulin Glargine	Phase 3 (in late-stage trials)
Liraglutide	Phase 3 (in late-stage trials)
Magnesium Oxide	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Rimonabant	Phase 3 (in late-stage trials)
Vildagliptin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Berberine, Bifidobacterium Spp., Cholecalciferol, Clindamycin, Empagliflozin, Exenatide, Melatonin, Mirabegron, Neomycin, Rosiglitazone, Simvastatin, Sitagliptin, Vancomycin.

Clinical trials & evidence

Clinical trials

Clinical trials: 630.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	533
PHASE4	33
PHASE2	30
PHASE3	16
PHASE1	6
PHASE1/PHASE2	5
PHASE2/PHASE3	4
EARLY_PHASE1	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03575000	PHASE4	NOT_YET_RECRUITING	Bromocriptine for Patients With Schizophrenia and Prediabetes
NCT03851627	PHASE4	RECRUITING	Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Overweight/Obese Men With T2DM or Prediabetes and Hypogonadism
NCT03938389	PHASE4	ACTIVE_NOT_RECRUITING	The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans
NCT05119179	PHASE4	RECRUITING	Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes
NCT05426525	PHASE4	ACTIVE_NOT_RECRUITING	Use of Empagliflozin to Treat Prediabetes
NCT05749874	PHASE4	ACTIVE_NOT_RECRUITING	Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
NCT06054035	PHASE4	RECRUITING	SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes
NCT06448130	PHASE4	NOT_YET_RECRUITING	Henagliflozin’s Impact on Prediabetes Remission
NCT06682351	PHASE4	NOT_YET_RECRUITING	Heterogeneity of Diabetes: Integrated Muli-Omics to Identify Physiologic Subphenotypes and Evaluate Targeted Prevention
NCT07254572	PHASE4	RECRUITING	Anti-atherosclerotic Efficacy of Selected Antidiabetic Drugs in Patients With Coronary Artery Disease and Pre-diabetes
NCT00579813	PHASE4	COMPLETED	Mechanisms Underlying Metabolic Syndrome in Obesity
NCT00928005	PHASE4	COMPLETED	Evaluating the Effects of a Diet and Exercise Program in People With Type 2 Diabetes or Prediabetes: (The SHAPE3 Study)
NCT01056497	PHASE4	COMPLETED	The Effect of A-lipoic Acid (ALA) on Fatty Acid-induced Impairment of Glucose-stimulated Insulin Secretion
NCT01436916	PHASE4	COMPLETED	Oral Cholecalciferol in Prevention of Type 2 Diabetes Mellitus
NCT01649219	PHASE4	UNKNOWN	Intensity of Exercise and Glucose Metabolism
NCT01765946	PHASE4	COMPLETED	Metformin and Longevity Genes in Prediabetes
NCT01960205	PHASE4	UNKNOWN	Effect of Saxagliptin on Pre-Diabetes Mellitus and Obesity
NCT01964703	PHASE4	COMPLETED	Effect of Rubus Occidentalis Extract on Plasma Glucose Levels in Subject With Prediabetes
NCT02104739	PHASE4	COMPLETED	Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
NCT02226510	PHASE4	COMPLETED	MetfoRmin and Its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease
NCT02700334	PHASE4	COMPLETED	Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients With Prediabetes
NCT02981121	PHASE4	UNKNOWN	Hospital-based Diabetes Prevention Study in Korea
NCT03006471	PHASE4	COMPLETED	Effect of Dapagliflozin on Blood Pressure Variability in Prediabetes and Prehypertension
NCT03029390	PHASE4	UNKNOWN	Effect of Berberine Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes
NCT03101930	PHASE4	COMPLETED	Cardiovascular Effects of GLP-1 Receptor Activation
NCT03398356	PHASE4	COMPLETED	Metformin and Its Impact on the Substances Associated With NO Production in Prediabetes Patients.
NCT03441750	PHASE4	COMPLETED	Efficacy of Metformin in Preventing Diabetes in China
NCT03774108	PHASE4	UNKNOWN	Metformin and Systemic Inflammation in HIV
NCT03917784	PHASE4	UNKNOWN	Effect of Oral Supplementation With Curcumin on Insulin Sensitivity in Subjects With Prediabetes
NCT04549415	PHASE4	COMPLETED	The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes
NCT04864860	PHASE4	UNKNOWN	Effect of Sea Weed (Ecklonia Cava Extract) on Blood Glucose and Insulin Level on Pre-diabetic Patients
NCT05786521	PHASE4	COMPLETED	Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Markers of Aging in Older Adults
NCT07462078	PHASE4	COMPLETED	The Effect of Lifestyle Modification on the Risk of Prediabetes Among Patients Attending Outpatient Clinic.
NCT05182970	PHASE3	RECRUITING	Metformin and Prevention of Cardiovascular Events in Patients With Acute Myocardial Infarction and Prediabetes (MIMET)
NCT07392151	PHASE3	NOT_YET_RECRUITING	Reversal to Normoglycemia by Treating Prediabetes
NCT07448974	PHASE3	NOT_YET_RECRUITING	Vitamin D and Type 2 Diabetes - Treat-To-Target
NCT00784433	PHASE3	COMPLETED	The CArdiovasCulAr Diabetes & Ethanol (CASCADE) Trial
NCT00967798	PHASE3	TERMINATED	Prevention of Cystic Fibrosis Diabetes
NCT00990184	PHASE3	COMPLETED	Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
NCT01574820	PHASE3	COMPLETED	Role of Rosiglitazone on Pre-Diabetes Mellitus and Coronary Artery Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BERBERINE	4	7
SAXAGLIPTIN ANHYDROUS	4	6
BROMOCRIPTINE	4	3
DAPAGLIFLOZIN	4	2
INSULIN GLARGINE	4	2
INULIN	4	2
ROSIGLITAZONE	4	2
ALCOHOL	4	1
CHOLECALCIFEROL	4	1
COLESEVELAM	4	1
DIOSMIN	4	1
EMPAGLIFLOZIN	4	1
ESTROGENS, CONJUGATED	4	1
ESZOPICLONE	4	1
EXENATIDE	4	1
FISH OIL	4	1
GLUCAGON	4	1
GLYCINE	4	1
LACTIC ACID	4	1
LIRAGLUTIDE	4	1
METFORMIN HYDROCHLORIDE	4	1
MIRABEGRON	4	1
PIOGLITAZONE	4	1
PRAMLINTIDE	4	1
ROFLUMILAST	4	1
SEMAGLUTIDE	4	1
SITAGLIPTIN	4	1
TESTOSTERONE UNDECANOATE	4	1
ZOPICLONE	4	1
POWDERED CELLULOSE	3	3