Glucose intolerance

Summary

Glucose intolerance (MONDO:0001076) is a disease with 1 cohort gene and 141 clinical trials. Top therapeutic interventions include rosiglitazone, berberine, and levocarnitine.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 141

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glucose intolerance
Mondo ID	MONDO:0001076
MeSH	D018149
DOID	DOID:10603
ICD-11	1392580302
NCIT	C34646
SNOMED CT	267426009
UMLS	C0271650
MedGen	75760
Is cancer (heuristic)	no

Also known as: glucose: [intolerance] or [malabsorption] · glucose: intolerance · glucose: malabsorption

Data availability: 1 ClinVar variant.

Disease family

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

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

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
9589	NC_012920.1(MT-TL1):m.3243A>G	MT-TL1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TL1	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TL1	Orphanet:324525	Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation
MT-TL1	Orphanet:480	Kearns-Sayre syndrome
MT-TL1	Orphanet:550	MELAS
MT-TL1	Orphanet:551	MERRF
MT-TL1	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia

Cohort genes → proteins

1 cohort genes, 0 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MT-TL1	HGNC:7490	ENSG00000209082		mitochondrially encoded tRNA-Leu (UUA/G) 1	clinvar

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MT-TL1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
frontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MT-TL1	118	ubiquitous	marker	frontal cortex, right frontal lobe, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MT-TL1	0

Structural data

PDB: 0 · AlphaFold-only: 0 · No structure: 1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Arginine	Phase 3 (in late-stage trials)
Liraglutide	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Rosiglitazone	Phase 3 (in late-stage trials)
Tadalafil	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cholecalciferol, Pioglitazone, Sitagliptin, Teplizumab, Vildagliptin.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MT-TL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MT-TL1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MT-TL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 141.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	110
PHASE3	10
PHASE4	9
PHASE1/PHASE2	3
PHASE2	3
PHASE1	3
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00301392	PHASE4	COMPLETED	Japan Prevention Trial of Diabetes by Pitavastatin in Patients With Impaired Glucose Tolerance (J-PREDICT)
NCT00319202	PHASE4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00740363	PHASE4	COMPLETED	Sitagliptin in Renal Transplant Recipients
NCT01017263	PHASE4	TERMINATED	Vyvanse and Glucose Intolerance in Children With Attention Deficit Hyperactivity Disorder (ADHD) and Obesity
NCT01497132	PHASE4	COMPLETED	Effects of Vitamin D on Beta Cell Function and Insulin Sensitivity in Pre-diabetes and Diabetes Mellitus Type 2
NCT02355509	PHASE4	COMPLETED	Effect of Acarbose on Postprandial Lipoprotein Levels in Glucose Intolerant Patients
NCT03809182	PHASE4	COMPLETED	Effect of Dexmedetomidine on Postoperative Glucose and Insulin Levels.
NCT04387201	PHASE4	COMPLETED	GLP-1 Therapy: The Role of IL-6 Signaling and Adipose Tissue Remodeling in Metabolic Response
NCT05050500	PHASE4	COMPLETED	Effects of Dapagliflozin on Inflammatory Factorslevel and Prognosis in Type 2 Diabetes With Acute Myocardial Infarction
NCT00004992	PHASE3	COMPLETED	Diabetes Prevention Program
NCT00240604	PHASE3	UNKNOWN	Prevention of Corticosteroid-induced Glucose Intolerance
NCT00412815	PHASE3	COMPLETED	Exercise Training, Insulin Resistance and Coronary Artery Disease
NCT00687466	PHASE3	UNKNOWN	Study on the Efficacy of Slow Release Insulin in Cystic Fibrosis Patients With Glucide Intolerance and Clinical Decay
NCT01394887	PHASE2/PHASE3	COMPLETED	Metformin & Inflammation in Pre-diabetic Children
NCT01436448	PHASE3	UNKNOWN	Probiotics (Lactobacillus Rhamnosus) in Reducing Glucose Intolerance During and After Pregnancy
NCT01444651	PHASE3	COMPLETED	A Trial of Tadalafil and Glycemic Traits
NCT01574820	PHASE3	COMPLETED	Role of Rosiglitazone on Pre-Diabetes Mellitus and Coronary Artery Disease
NCT01586442	PHASE3	COMPLETED	Comparison of Eplerenone Versus Spironolactone in Heart Failure Patients With Glucose Intolerance or Type 2 Diabetes
NCT02291458	PHASE3	UNKNOWN	L-arginine and Brown Adipose Tissue
NCT04860063	PHASE3	UNKNOWN	Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH.
NCT00436475	PHASE1/PHASE2	COMPLETED	Vitamin D and Calcium Homeostasis for Prevention of Type 2 Diabetes
NCT01405911	PHASE2	COMPLETED	Dose Response Finding Study of MK-0431/ONO-5435 in Japanese Subjects With Impaired Glucose Tolerance (MK-0431-105)
NCT02095873	PHASE1/PHASE2	COMPLETED	Healthy Aging Through Functional Food
NCT03864068	PHASE2	COMPLETED	Inositol Supplementation to Treat PCOS (INSUPP-PCOS)
NCT04062890	PHASE2	WITHDRAWN	Inhibiting GABA Transaminase to Relieve Obesity Induced Hyperinsulinemia and Insulin Resistance
NCT05468229	PHASE1/PHASE2	UNKNOWN	Dorzagliatin and 1st Phase Insulin and Beta-cell Glucose Sensitivity in IGT and NGT
NCT01887691	PHASE1	TERMINATED	Sleep Effectiveness and Insulin and Glucose Homeostasis
NCT03023891	PHASE1	COMPLETED	Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids
NCT03201952	PHASE1	TERMINATED	Examination of the Metabolic Effects of Direct Bile Salt Delivery to the Ileum in Humans
NCT02346149	EARLY_PHASE1	COMPLETED	Effect of Acute Hyperglycemia on Renal Tissue Oxygenation
NCT02412995	EARLY_PHASE1	COMPLETED	The Effects of Sea Buckthorn and Strawberry on Postprandial Glycaemia, Insulinemia and Appetite
NCT01129297	Not specified	RECRUITING	A Biological Atlas of Severe Obesity (Biological Tissue Collection)
NCT04008147	Not specified	RECRUITING	Hepcidin and Glucose Metabolism
NCT04234373	Not specified	ACTIVE_NOT_RECRUITING	Effect of a Low-carb Dietary Intervention in Obese Patients: a Pilot Trial
NCT04737200	Not specified	RECRUITING	The Impact of Overnight Nutrition Support on Sleep and Circadian Rhythm Disruption in the ICU
NCT04943926	Not specified	RECRUITING	Dietary Strategies for Remission of Type 2 Diabetes
NCT05121844	Not specified	ACTIVE_NOT_RECRUITING	Use of Continuous Glucose Monitoring in Non-Diabetic Population to Compliment Signos Mobile Health Platform
NCT05121935	Not specified	NOT_YET_RECRUITING	MAL-ED Metabolic: A Follow-Up of Chronic Disease at Puberty
NCT05468255	Not specified	RECRUITING	The Impact of Removal of Exercise on Glycemic Control and Vascular Health in Older Active Adults
NCT05544266	Not specified	RECRUITING	Rare and Atypical Diabetes Network

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROSIGLITAZONE	4	4
BERBERINE	4	3
LEVOCARNITINE	4	2
SITAGLIPTIN	4	2
URSODIOL	4	2
ACARBOSE	4	1
ACETIC ACID	4	1
ANAKINRA	4	1
CHOLECALCIFEROL	4	1
CYANOCOBALAMIN	4	1
DAPAGLIFLOZIN	4	1
DULAGLUTIDE	4	1
EPLERENONE	4	1
ESZOPICLONE	4	1
FERROUS FUMARATE	4	1
MORPHINE SULFATE	4	1
SPIRONOLACTONE	4	1
TADALAFIL	4	1
VIGABATRIN	4	1
ZOPICLONE	4	1
INOSITOL	3	2
ARGININE	3	1
ASPARTAME	3	1
CANDESARTAN	3	1
CARNITINE	3	1
DORZAGLIATIN	3	1
SACCHARIN	3	1
SELENIUM	3	1
SUCRALOSE	3	1
TAGATOSE	3	1