Type 2 diabetes mellitus
Chronic carbohydrate metabolism disorder driven by insulin resistance and relative insulin deficiency. Associated with increased cardiovascular risk and microvascular complications.
ICD-10 E1128 drugs
Also known as: T2DM, T2D, Non-insulin-dependent diabetes mellitus, NIDDM
Drugs used for this condition
- ADapagliflozinFirst line · Sodium-glucose cotransporter-2 (SGLT2) inhibitorFirst-line for type 2 diabetes per ADA/EASD 2024 and SED 2023, on par with metformin in patients with established cardiovascular or renal disease. Dose 10 mg once daily. DECLARE-TIMI 58 (2019) showed 17% reduction in cardiovascular death or HF hospitalization and 24% reduction in renal progression in T2D patients with risk factors. Can be added to metformin, ACE-I, ARB, statins.
- AEmpagliflozinFirst line · Sodium-glucose co-transporter 2 inhibitors (SGLT2i)Per ADA 2024 and EASD 2022, empagliflozin and other SGLT2 inhibitors are first-line in T2D patients with established ASCVD, HF (reduced or preserved EF), or CKD. Prescribed independently of HbA1c and of concurrent metformin therapy. Start 10 mg once daily; titrate to 25 mg if glycemic control is inadequate.
- AGliclazideSecond line · SulfonylureasType 2 diabetes with inadequate glycemic control on metformin. Starting dose Diamicron MR 30 mg once daily with breakfast; titrate up to 120 mg. ADA 2024 and Spanish redGDPS 2023 position sulfonylureas as third-line after metformin and SGLT-2 inhibitors or GLP-1 agonists, especially in patients with cardiovascular comorbidities. Gliclazide MR has lower severe hypoglycemia and cardiovascular mortality risk than glibenclamide (ADVANCE trial).
- ALinagliptinSecond line · Dipeptidyl peptidase 4 (DPP-4) inhibitor – gliptinLinagliptin is second-line DPP-4 inhibitor for type 2 diabetes. redGDPS 2024 recommends linagliptin as an option in patients with chronic kidney disease (eGFR below 45 mL/min) when metformin is contraindicated and a drug without dose adjustment is needed. No significant cardiovascular risk reduction (neutral profile per CARMELINA 2018).
- ALiraglutideFirst line · Glucagon-like peptide-1 (GLP-1) receptor agonistFirst-line in type 2 diabetes alongside metformin in patients with established cardiovascular disease per ADA/EASD 2024 and SED 2023. Reduces HbA1c by 1.0–1.5%, lowers weight by 2–4 kg, and cuts cardiovascular events. Start at 0.6 mg subcutaneously once daily and titrate to 1.8 mg over 1–2 weeks. With more convenient and effective analogues (semaglutide, tirzepatide), liraglutide is partly losing its first-choice place.
- AMetforminFirst line · Biguanides. Oral antihyperglycemic agentsFirst-line pharmacological treatment for type 2 diabetes in adults. Lowers HbA1c by 1.0–1.5% as monotherapy, supports weight reduction or weight neutrality, and does not cause hypoglycemia as monotherapy. ADA 2024, ADA/EASD 2022, and NICE NG28 list metformin as the baseline agent in the absence of contraindications. Combinations with SGLT2 inhibitors or GLP-1 receptor agonists are built around individual cardiovascular and renal risk.
- ASemaglutideFirst line · GLP-1 receptor agonistsPer ADA 2024 and EASD 2022, semaglutide is first-line in T2D with established CVD, HF, or CKD, especially when weight loss is needed. Subcutaneous start: 0.25 mg weekly for 4 weeks, then 0.5 mg, escalating to 1.0 or 2.0 mg if needed. SUSTAIN-6 (3,297 patients) showed a 26 % reduction in MACE in T2D patients at high CV risk.
- ASitagliptin + MetforminSecond line · Fixed-dose combination: DPP-4 inhibitor plus biguanideType 2 diabetes in adults with HbA1c above target on metformin monotherapy. Per ADA/EASD 2024 and redGDPS 2024, second-line when ASCVD, HF, and CKD are absent. Dose: 50/850, 50/1000 mg twice daily with meals (Janumet) or 100/1000 mg once daily (Janumet XR). HbA1c at 3 months. With ASCVD, HFrEF, or CKD, GLP-1 RA or SGLT2 inhibitor takes priority.
- ATirzepatideFirst line · Blood glucose lowering drugs, GLP-1 and GIP receptor agonistsTirzepatide is first-line therapy for type 2 diabetes, particularly with co-existing obesity. The SURPASS programme (n>13,000) demonstrated superiority over all comparators: SURPASS-2 vs semaglutide 1 mg (Frias 2021, HbA1c reduction 2.0–2.3% vs 1.9%), SURPASS-3 vs insulin degludec (Ludvik 2021), SURPASS-4 vs insulin glargine (Del Prato 2021), SURPASS-5 (Dahl 2022), and the SURPASS-CVOT cardiovascular outcomes trial. Average HbA1c reduction 2.0–2.6%, weight loss 5–15 kg at 10–15 mg/week. ADA 2024 and EASD 2022 guidelines list tirzepatide as preferred in obesity and cardiovascular risk. Not registered in Russia as of 2026-05-20; available via personal import programmes.
- AVildagliptin + MetforminSecond line · Fixed-dose combination: DPP-4 inhibitor plus biguanideType 2 diabetes in adults with HbA1c above target (usually <7%, <7.5–8% in older patients) on metformin monotherapy. Per ADA/EASD 2024 and redGDPS 2024, DPP-4 + metformin is one second-line option when ASCVD, HF, or CKD is absent (otherwise GLP-1 RA or SGLT2 inhibitors take priority). Dose: 50/850, 50/1000 mg twice daily with meals. Check HbA1c at 3 months. Combination strength – weight-neutral and low hypoglycemia risk.
- BGlibenclamideSecond line · Oral hypoglycemic agents. SulfonylureasGlibenclamide is a long-experienced sulfonylurea oral hypoglycemic agent. Reduces HbA1c by 1.0–1.5% as monotherapy. ADA 2024 and ADA/EASD 2022 do not recommend sulfonylureas as first choice in T2D due to increased hypoglycemia risk and lack of cardiovascular benefit. Metformin, SGLT2 inhibitors and GLP-1 RAs are preferred. Glibenclamide remains on the market as a low-cost alternative when modern drugs are not accessible.
- BGlimepirideSecond line · Third-generation sulfonylureaType 2 diabetes in adults with preserved beta-cell function, when HbA1c is above target on metformin monotherapy. Per ADA/EASD 2024 and redGDPS 2024, sulfonylureas are a second-line option in patients with limited access to newer classes (GLP-1 RA, SGLT2 inhibitors) or when rapid HbA1c reduction is needed. With ASCVD, HF, or CKD – GLP-1 RA or SGLT2 inhibitor takes priority. Dose: 1–6 mg once daily with breakfast. Effect at 1–2 weeks.
- BPioglitazoneThird line · Thiazolidinedione (PPAR-γ agonist), oral antidiabeticOral antidiabetic for type 2 diabetes. The redGDPS 2024 algorithm positions pioglitazone as a third-line option after metformin and GLP-1 RA / SGLT-2i in insulin-resistant patients, particularly with concomitant non-alcoholic fatty liver disease. In Spanish practice it is used less than GLP-1 agonists because of weight gain, oedema, heart failure and fracture risk. PROactive 2005 showed a 16% reduction in a composite cardiovascular endpoint but no significant effect on the primary endpoint.
- BRepaglinideSecond line · Meglitinide – short-acting oral insulin secretagogueSecond-line in T2D per ADA/EASD 2024 and SED 2023. Used in patients with irregular meals or intolerance to metformin or sulfonylureas. Dose 0.5–4 mg before each meal. Particularly useful in CKD – no accumulation with reduced eGFR (advantage over sulfonylureas). Skip the dose if a meal is skipped – lower hypoglycemia risk.
- BSitagliptinSecond line · Dipeptidyl peptidase-4 (DPP-4) inhibitorSecond-line in type 2 diabetes per ADA/EASD 2024 and SED 2023. First-line is metformin combined with GLP-1 agonists and/or SGLT2 inhibitors when cardiovascular or renal disease is present. Sitagliptin is considered as add-on to metformin in patients without major cardiovascular risk and without obesity, where tolerability and low hypoglycemia risk are priorities. In TECOS, it did not raise heart failure hospitalization risk in T2D patients with cardiovascular disease (unlike saxagliptin).
- BVildagliptinSecond line · Dipeptidyl peptidase-4 (DPP-4) inhibitorSecond-line in T2D per ADA/EASD 2024 and SED 2023 as metformin add-on or in triple therapy. Dose 50 mg twice daily. Reduces HbA1c by 0.5–0.8% without hypoglycemia or weight effect. Compared with sitagliptin, no significant efficacy advantage; choice depends on cost and availability.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- DAlpha-lipoic acid (thioctic acid, ALA)Not recommended · Antioxidant; cofactor of pyruvate and α-ketoglutarate dehydrogenaseALA is marketed as a glucose-lowering drug that can replace metformin. ADA Standards of Care 2024 do not recommend it for glycaemic control: a meta-analysis of RCTs (Akbari 2018) shows a statistically significant but clinically small reduction in HbA1c, insufficient to replace glucose-lowering therapy. AEMPS registered the drug only for polyneuropathy, not for diabetes itself. Replacing metformin or insulin with ALA leads to decompensation and ketoacidosis risk. Concerns about glycaemic control require regimen review with an endocrinologist, not supplement self-prescription.
- DArtichoke (Cynara scolymus)Not recommended · Herbal preparation, supplement. In EU – traditional herbal medicinal product (EMA HMPC). In Russia OTC product Hofitol is registeredArtichoke (Cynara scolymus, cynara) is a plant extract promoted as a supplement to lower blood sugar and improve metabolism in type 2 diabetes. It has not shown convincing benefit for this use: there is no evidence base confirming an effect of artichoke on glucose levels or the course of diabetes. Type 2 diabetes is managed through diet, physical activity, weight reduction, and medicines prescribed by a doctor (such as metformin), with regular glucose monitoring. Artichoke should not replace treatment with proven benefit – dropping it for the supplement risks missed care.
- DBerberineNot recommended · Dietary supplements, plant alkaloids (local classification)Berberine is a plant alkaloid sold as a supplement to lower blood sugar in type 2 diabetes. Its benefit for this use has not been convincingly shown – there is no solid evidence behind the claim. Blood sugar in type 2 diabetes is reliably managed with changes to diet and physical activity, and where needed with medicines a doctor prescribes, such as metformin.
- DBlack seed (Nigella sativa)Not recommended · Botanical supplement, black seed oil (Nigella sativa, thymoquinone); no EMA HMPC monographBlack seed is actively marketed as a «natural insulin alternative» and a remedy «instead of metformin». The Hadi 2021 meta-analysis (Pharmacol Res) of 16 RCTs in type 2 diabetes reported fasting glucose reductions of about 17 mg/dL and HbA1c reductions of about 0.5%. The effect resembles a weak metformin dose, but methodology limits the conclusion: trials are short (8–12 weeks), populations are heterogeneous, doses ranged from 1 to 3 g/day, and most studies kept metformin and insulin in place – so the black-seed effect is additive. RCTs with hard endpoints (micro- and macrovascular complications, mortality) have not been performed. ADA Standards of Care 2024 recommend metformin as first-line in most patients with type 2 diabetes, adding an SGLT2 inhibitor (empagliflozin, dapagliflozin) or GLP-1 receptor agonist (semaglutide, dulaglutide, liraglutide) in heart failure, chronic kidney disease, or atherosclerotic cardiovascular disease, and basal insulin at HbA1c above 10%. The Spanish redGDPS holds the same approach. Replacing metformin or insulin with black seed in type 2 diabetes worsens glycaemia and risks retinopathy, nephropathy, neuropathy, and cardiovascular events. If black seed was recommended as a substitute, consider seeking a second opinion – glycaemic targets in type 2 diabetes are reached with proven drugs.
- DChromium picolinateNot recommended · Trace mineral, supplement marketed for blood sugar control and weight lossChromium picolinate is marketed as a «blood-sugar support». Meta-analyses of HbA1c in type 2 diabetes are inconsistent: some RCTs show a 0.2–0.6 % reduction, others none. Trial quality is low, chromium doses and forms vary, follow-up is short. ADA Standards of Care 2024 and the Spanish redGDPS 2023 do not recommend chromium for type 2 diabetes because of weak and conflicting evidence. Proven options in type 2 diabetes are metformin, GLP-1 agonists, SGLT2 inhibitors, dietary change and physical activity. If chromium was prescribed instead of or in addition to these, consider seeking a second opinion from an endocrinologist.
- DD-chiro-inositolNot recommended · Inositol stereoisomer, supplement. Usually used combined with myo-inositol in 40:1 ratioD-chiro-inositol is an inositol isomer sold as a supplement and promoted for blood sugar control and better insulin sensitivity. For type 2 diabetes the convincing benefit has not been shown: there is no evidence base for this use, and the available data are weak and do not confirm an effect on glucose or HbA1c. What helps type 2 diabetes is changes to diet and weight, regular physical activity, and medicines with an established evidence base such as metformin. The compound itself is harmless in this role, but it should not replace prescribed treatment.
- DHoly basil, tulsi (Ocimum sanctum, Ocimum tenuiflorum)Not recommended · Plant adaptogen from Ayurvedic medicine, supplement. Not registered as medicine in EU or AEMPSHoly basil, or tulsi (Ocimum sanctum), is a plant from Ayurveda sold as a supplement to lower blood sugar in type 2 diabetes. Studies have not shown a convincing benefit for this use, and the evidence base for taking tulsi in type 2 diabetes is lacking. Blood sugar drops reliably with changes to diet, physical activity, weight loss and medications of proven effectiveness that a doctor selects.
- DInulin (chicory/agave/Jerusalem artichoke prebiotic)Not recommended · Soluble fructan fibre, prebiotic. Supplement in Russia and Spain. EFSA approved health claim for chicory inulin on maintenance of normal defecation (2015). AEMPS does not register it as a medicineInulin is offered in type 2 diabetes as a «natural sugar control». Small RCTs showed modest postprandial glycaemia and HbA1c reductions (by 0.2–0.4%) on inulin 10–20 g/day. Effect is modest, not comparable to glucose-lowering pharmacotherapy. ADA Standards of Care 2024 in T2DM list metformin + lifestyle modification first-line; if HbA1c >7.5% or established cardiovascular or kidney disease, obesity – GLP-1 agonists (semaglutide, dulaglutide) or SGLT-2 inhibitors (empagliflozin, dapagliflozin) with confirmed cardio- and nephroprotection. Inulin is not in international T2DM guidelines. If inulin was recommended as a substitute for metformin or GLP-1 agonists in a patient with confirmed T2DM, consider seeking a second opinion from an endocrinologist.
- DMyo-inositolNot recommended · Inositol stereoisomer, supplement. Has evidence base in polycystic ovary syndrome (PCOS)Myo-inositol is sold for «natural blood sugar control» on the insulin signalling improvement hypothesis. Evidence in confirmed T2DM is weak: no quality RCTs with HbA1c, cardiovascular event or microvascular complication endpoints. ADA Standards of Care 2024 for T2DM lists metformin first-line, then SGLT2i and GLP-1 RA per cardiovascular and renal risk; myo-inositol is in no international diabetes guideline. In PCOS patients with insulin resistance the effect is described above; in patients with confirmed T2DM without PCOS replacing standard therapy with myo-inositol is not justified. If myo-inositol was recommended for T2DM instead of metformin, consider seeking a second opinion from an endocrinologist.
- DPsyllium (Plantago ovata, ispaghula husk)Not recommended · Soluble and insoluble fibre from seed husk. AEMPS registered Plantaben and Cenat as medicinal products for chronic constipation and maintenance of normal defecation. ACG 2014 and NICE NG61 IBS 2017 list psyllium as the primary soluble fibrePsyllium is offered in type 2 diabetes as a «natural sugar control». Gibb 2015 meta-analysis (35 RCTs, 1377 patients) showed moderate HbA1c reduction (by 0.4–0.6%) and postprandial glycaemia on psyllium 10–20 g/day × 12 weeks. Effect is modest, not comparable to glucose-lowering pharmacotherapy. ADA Standards of Care 2024 in T2DM list metformin + lifestyle modification first-line; if HbA1c >7.5% or comorbid CVD, kidney disease, obesity – GLP-1 agonists (semaglutide, dulaglutide) or SGLT-2 inhibitors. Psyllium may be used as adjunct for moderate additional HbA1c reduction in patients with hypercholesterolaemia and T2DM but not as substitute for metformin or GLP-1 agonist. If psyllium was recommended as a substitute for standard glucose-lowering therapy, consider seeking a second opinion from an endocrinologist.
- DPycnogenol (French maritime pine bark extract, Pinus pinaster)Not recommended · Plant polyphenol complex, supplement. Standardised maritime pine bark extract with 65–75% oligomeric proanthocyanidinsPycnogenol is sold as a supplement for type 2 diabetes and diabetic retinopathy. Mijnhout 2012 systematic review of 6 RCTs in 528 patients showed moderate HbA1c reduction (−0.3–0.5%) at 100–200 mg/day, less than first-line metformin (HbA1c −1–1.5%). In diabetic retinopathy small RCTs recorded retinal microcirculation improvement, but clinical endpoints (vision loss, laser photocoagulation) were not assessed. ADA 2024 lists metformin + lifestyle change (DASH/Mediterranean diet, 150 min/week physical activity) first-line in type 2 diabetes; with cardiovascular risk – SGLT-2 inhibitors and GLP-1 agonists. If pycnogenol was recommended as a metformin substitute or instead of glycaemic control, consider seeking a second opinion from an endocrinologist.
- DTaurineNot recommended · Sulfur-containing amino acid, supplement and energy-drink ingredient. In Russia registered as a medicine (Dibicor) for T2DM and CHFTaurine is registered in Russia as the medicine Dibicor for T2DM (250–500 mg twice daily) – one of the specific Russian uses, registered nowhere else in Europe or the US. Evidence base: several small RCTs by Russian authors with HbA1c and fasting glucose endpoints, not confirmed in large international trials. ADA Standards of Care 2024 and redGDPS list metformin first-line for T2DM, then SGLT2i and GLP-1 RA; taurine is in no international diabetes guideline. AEMPS and EMA do not approve taurine for T2DM. If taurine was recommended for T2DM as a metformin substitute, consider seeking a second opinion.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit