SGLT2 Inhibitors
18 drugsAbout SGLT2
SGLT2 (Sodium-Glucose Co-Transporter 2) is a protein in the kidneys responsible for glucose reabsorption. By inhibiting SGLT2, excess glucose is excreted through urine, lowering blood sugar levels. This mechanism has made it a significant drug target for metabolic diseases.
Human genetic studies provide strong validation for SGLT2 as a therapeutic target (max score 0.94). Loss-of-function variants are associated with increased risk of carbohydrate metabolism disorders and familial renal glucosuria. Activation of SGLT2 is likely beneficial based on genetic evidence.
SGLT2 is targeted by 15 FDA-approved small molecule drugs, including FARXIGA, STEGLATRO and INVOKANA. These drugs are developed by 6 companies, including Boehringer Ingelheim, AstraZeneca, and Johnson & Johnson. The target spans metabolic and cardiovascular indications.
SGLT2 Genetic Evidence Strong
SGLT2 has strong genetic support with a maximum score of 0.94 linking it to carbohydrate metabolism disorders.
Strong genetic support suggests a higher probability of clinical success for SGLT2-targeting drugs.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 3 traits
- • Strong signal in nutritional or metabolic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
8 totalGWAS and other genetic studies link SLC5A2 to 8 diseases.
Loss-of-function causes disease; activation may help
Loss-of-function causes disease; activation may help
Effect Sizes
Genetic effect on disease risk. OR<1 or β<0 = loss-of-function is protective (inhibiting target may help).
🔗 Colocalization Evidence 8 strong
max H4: 0.99eQTL/pQTL signals for SLC5A2 colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top SGLT2 Drugs
Six companies have approved SGLT2-targeting drugs, with Boehringer Ingelheim, AstraZeneca, and Johnson & Johnson as top players.
The competitive landscape indicates moderate market concentration, suggesting potential entry barriers for new companies.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| INVOKAMET XR | Johnson & Johnson | 2016 | 4 |
| FARXIGA | AstraZeneca | 2014 | 3 |
| XIGDUO XR | AstraZeneca | 2014 | 3 |
| SYNJARDY XR | Boehringer Ingelheim | 2016 | 3 |
| INVOKANA | Johnson & Johnson | 2013 | 3 |
| SYNJARDY | Boehringer Ingelheim | 2015 | 3 |
| BRENZAVVY | THERACOSBIO | 2023 | 1 |
| STEGLATRO | Merck | 2017 | 1 |
| GLYXAMBI | Boehringer Ingelheim | 2015 | 1 |
| SEGLUROMET | Merck | 2017 | 1 |
| TRIJARDY XR | Boehringer Ingelheim | 2020 | 1 |
| STEGLUJAN | Merck | 2017 | 1 |
| DAPAGLIFLOZIN | Apotex | 2026 | - |
| DAPAGLIFLOZIN AND METFORMIN HYDROCHLORIDE | MSN | 2026 | - |
| DAPAGLIFLOZIN AND SAXAGLIPTIN HYDROCHLORIDE | TORRENT | 2026 | - |
SGLT2 Drug Modality Landscape
Modalities
Routes of Administration
SGLT2 is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests a whitespace opportunity for alternative modalities like antibodies or fusion proteins.
SGLT2 Clinical Trials 934 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on SGLT2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 220 | 185 | 6 | 29 | 97% |
| Phase 2 | 202 | 99 | 23 | 80 | 81% |
| Phase 3 | 241 | 154 | 17 | 69 | 90% |
| Phase 4 | 271 | 162 | 29 | 79 | 85% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved SGLT2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting SGLT2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
SGLT2 Drug Approval Timeline (2013 - 2023)
The first SGLT2 inhibitor, INVOKANA, was approved in 2013, and the most recent, BRENZAVVY, in 2023.
The 11-year approval span suggests a mature market with potential for incremental innovation rather than disruptive breakthroughs.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 9 companies competing
- • Market share by company
Full Drug Portfolio
- • All 18 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 18-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 356 (53 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on SGLT2. A trial counts if an approved drug acting on SGLT2 is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.