Table 1.
Targets and Potential Utility of Diabetes Therapies in Conditions of the Diabetes Syndrome
| DM Therapy | Effect on “Egregious Eleven” (Mechanisms of Hyperglycemia) | Potential Utility in Diabetes Syndrome Conditions | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Islet Regulation | Insulin Resistance | Brain (↑ Appetite, ↓Morning Dopamine Surge, ↑ Sympathetic Tone) | Colon/Biome (Abnormal Microbiome, Possible ↓ GLP-1 Secretion) | Immune Dysreg/Inflammation | Stomach/Small Intestine (↑Rate of Glucose Absorption) | Kidney (↑Glucose Re-Absorption) | ||||||
| β-Cell (↓Function, Mass; ↓ Insulin, ↓Amylin) | Incretin Defect | α-Cell (↓ Glucagon) | Liver (↑ Glucose Production) | Adipose (↑ Lipolysis) | Muscle (↓ Peripheral Insulin Uptake) | |||||||
| TZDs | ✔ | ✔ | ✔ | ✔ | ✔ | Cancer | ||||||
| Dementia | ||||||||||||
| Psoriasis | ||||||||||||
| ASCVD | ||||||||||||
| NAFLD/NASH | ||||||||||||
| Metformin | ✔ | ✔ | Cancer | |||||||||
| Dementia | ||||||||||||
| ASCVD | ||||||||||||
| NAFLD/NASH | ||||||||||||
| GLP-1 RAs | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | Cancer | ||
| Dementia | ||||||||||||
| ASCVD | ||||||||||||
| NAFLD/NASH | ||||||||||||
| DPP-4 inhibitors | ✔ | ✔ | ✔ | ✔ | Dementia | |||||||
| NAFLD/NASH | ||||||||||||
| SGLT-2 inhibitors | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ASCVD | |||||
| NAFLD/NASH | ||||||||||||
| Dopamine D2 agonist | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ✔ | ASCVD | ||||
| Immune modulators* | ✔ | ✔ | Psoriasis | |||||||||
Note: *Used but not approved for DM.
Abbreviations: ASCVD, atherosclerotic cardiovascular disease; DM, diabetes mellitus; DPP, dipeptidyl peptidase; GLP, glucagon-like protein; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; RA, receptor agonist; SGLT, sodium-glucose cotransporters; TZD, thiazolidinediones.