Salsalate: The Non-Acetylated Salicylate

Table of Contents

1. What Salsalate Is
2. How Salsalate Differs From Aspirin
3. Stomach and Bleeding Findings
4. The Label and Its US Regulatory Status
5. Arthritis Trials
6. Blood Sugar: The TINSAL-T2D Trials
7. Prediabetes and Insulin Resistance Studies
8. Heart and Blood Vessel Findings
9. Tau, Alzheimer's Disease and Progressive Supranuclear Palsy
10. Side Effects Seen in the Trials
11. Label Warnings and Interactions
12. What Is Not Known
13. Key Research Papers
14. Connections
15. Featured Videos

What Salsalate Is

The chemical name of salsalate is salicylsalicylic acid. The prescribing label describes it as "a dimer of salicylic acid", meaning two salicylic acid units linked by an ester bond. It is a prodrug: the tablet itself does little until the body breaks it apart.

The label explains the journey. Salsalate barely dissolves in stomach acid (less than 0.1 milligram per millilitre at the acidity of the stomach) but dissolves readily in the small intestine, where part of it is split into two molecules of salicylic acid. A large share is absorbed whole and is then split by enzymes in the body; the intact molecule has a half-life of about one hour. About 13% leaves through the kidneys still joined together, attached to glucuronic acid. Because of that lost share, the label states that salsalate delivers about 15% less salicylic acid than aspirin when the two are compared on an equal salicylic-acid basis (3.6 grams of salsalate against 5 grams of aspirin).

A 1983 crossover study in six people with rheumatoid arthritis, who took equal molar doses of salsalate and aspirin, found the same thing directly: absorption was similar, but the amount of salicylic acid reaching the blood was lower after salsalate. The authors traced this to incomplete splitting, with the unsplit salsalate excreted mainly as glucuronide conjugates.

Once salicylic acid is in the blood, the body's ability to clear it becomes saturated at anti-inflammatory doses. The label states that the half-life of salicylic acid then rises from 3.5 hours to 16 hours or more. The label states that, because of this, twice-daily dosing holds blood levels in the target range of 10 to 30 milligrams per 100 millilitres.

How Salsalate Differs From Aspirin

Aspirin is acetylsalicylic acid: salicylic acid with an acetyl group attached. That acetyl group is passed onto the enzyme cyclooxygenase in platelets and blocks it permanently. A platelet cannot make new enzyme, so one dose of aspirin dampens clotting for the platelet's whole life of about a week to ten days. This is the effect behind low-dose aspirin for heart disease, and also behind aspirin's bleeding risk. The Aspirin page covers it in detail.

Salsalate carries no acetyl group. Its salicylic acid is only a weak, reversible blocker of cyclooxygenase in the test tube; the label calls it "a weak inhibitor of prostaglandin synthesis in vitro", while noting that salsalate appears to reduce prostaglandin production selectively in the body. The practical differences reported in studies are:

• Platelets. The label states that "unlike aspirin, salsalate does not inhibit platelet aggregation." A 1991 study gave salsalate to 12 healthy adults and 9 people with haemophilia A, an inherited bleeding disorder. Neither group showed any lengthening of bleeding time or any change in platelet clumping in response to the usual laboratory triggers. The authors suggested the drug might be useful for arthritis in people with inherited clotting disorders.
• Stomach prostaglandins. Prostaglandins help protect the stomach lining. In a 1990 study in healthy volunteers, aspirin cut the prostaglandin content of the stomach and duodenal lining by more than 90%, while salsalate produced no significant change (details in the next section).
• Inflammation. A 1989 multicentre trial in rheumatoid arthritis set out to ask whether the acetyl group adds anything to salicylic acid's anti-inflammatory effect. It found the two drugs equally effective, which led the authors to conclude that the acetyl group does not add anti-inflammatory power.

So the two drugs share their active product, salicylic acid, and share its anti-inflammatory and blood-sugar effects and its toxicity at high levels. They differ in what the acetyl group adds: the permanent platelet block and much of the stomach injury.

Stomach and Bleeding Findings

Several studies from the 1980s and 1990s used endoscopy (a camera passed into the stomach) to compare salsalate with other anti-inflammatory drugs:

• Salsalate against aspirin, healthy volunteers (1990). People took salsalate 3.0 grams a day, aspirin 3.9 grams a day, or a placebo for seven and a half days. Blood salicylate levels with the two drugs were nearly identical, at about 15 milligrams per 100 millilitres. On endoscopy, the salsalate and placebo groups showed minimal injury, while the aspirin group had considerable injury in the stomach and duodenum. Aspirin lowered blood prostaglandin F2-alpha by 58%; salsalate lowered it by 11%.
• Salsalate against naproxen, rheumatoid arthritis (1990). Over three months, 8 of 21 people taking naproxen (38%) developed active ulcers or widespread erosions, compared with none of 18 people taking salsalate. Five of the eight naproxen patients with damage had no symptoms at the time. The main drawback recorded for salsalate was ear problems, which accounted for six of its nine withdrawals.
• Salsalate against aspirin, rheumatoid arthritis (1989). In the 233-patient multicentre trial, severe digestive problems were more frequent with aspirin.

The label adds that, in contrast to aspirin, salsalate "causes no greater fecal gastrointestinal blood loss than placebo." The same label, however, still carries the full warning that applies to the whole class of non-steroidal anti-inflammatory drugs (NSAIDs): that these drugs can cause bleeding, ulcers and perforation of the stomach or intestines, which can be fatal and can occur without warning symptoms. Spontaneous reports listed on the label include gastrointestinal bleeding. The studies above were small and short, and they measured visible damage rather than hospital admissions for bleeding.

The Label and Its US Regulatory Status

The current prescribing label on DailyMed, the National Library of Medicine's label database, states that salsalate "is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder." It is a prescription-only tablet, made in 500 milligram and 750 milligram strengths.

On dosing, the label states that the usual adult dose is 3,000 milligrams a day, split into two or three doses, that some people, such as older adults, may need less, and that full benefit may not appear for 3 to 4 days, when blood salicylate levels reach a steady state. It states that dosage recommendations for children have not been established.

The regulatory status is unusual. Salsalate has a long history of use (the label's references date back to the 1970s), but the DailyMed salsalate tablet records checked for this page list its marketing category as "unapproved drug other", the category used for prescription drugs marketed without an approved new drug application. In other words, these tablets are listed as sold without a completed FDA approval of the product for its labelled use. The labels nonetheless follow the standard format for the anti-inflammatory drug class, including its boxed warning on heart and stomach risks, and they are dispensed with the class's medication guide. Salsalate has never been approved for diabetes or any other use outside arthritis; the diabetes research below was done under research protocols.

Arthritis Trials

Salsalate's place in arthritis rests on head-to-head trials against other anti-inflammatory drugs:

• Against aspirin (1989). 233 people with rheumatoid arthritis whose disease had flared were randomly given salsalate (starting at 3 grams a day) or aspirin (starting at 3.6 grams a day) for 12 weeks, with doses adjusted over the first 5 weeks. 150 people finished. The two treatments were equally effective on all the usual measures, and severe gastrointestinal problems were more frequent with aspirin.
• Against diclofenac (1995). 301 people with rheumatoid arthritis from 16 centres were randomised to salsalate or diclofenac for 8 weeks after their usual anti-inflammatory drug was withdrawn and their disease flared. The average settled doses were 3.55 grams a day of salsalate and 112 milligrams a day of diclofenac. Both groups improved substantially from the flare, with no statistically significant or clinically important difference between them. More people stopped salsalate because of side effects (19 against 9), mainly tinnitus and hearing loss.

The label itself does not cite trials in osteoarthritis by name; its references are to rheumatoid arthritis studies and to older work on salicylic acid in arthritis. The Rheumatoid Arthritis and Osteoarthritis pages cover the conditions and their other treatments.

Blood Sugar: The TINSAL-T2D Trials

That salicylates lower blood sugar is an old observation. A 2010 systematic review notes that salicylates were shown more than a century ago to lower glucose in people with diabetes, and that many laboratory and animal studies support the effect. The modern idea is that long-running, low-grade inflammation helps cause insulin resistance, and that high-dose salicylate damps one of the main inflammation switches in cells, a protein complex called nuclear factor kappa B.

The US National Institutes of Health funded the main test, called TINSAL-T2D (Targeting Inflammation Using Salsalate in Type 2 Diabetes). It was done in two stages. Haemoglobin A1c, the blood test that reflects average blood sugar over about three months, was the main measure in both.

Stage 1: three doses for 14 weeks (2010)

Adults with type 2 diabetes whose haemoglobin A1c was 7.0% to 9.5% on diet, exercise and tablets were randomised to placebo or salsalate at 3.0, 3.5 or 4.0 grams a day for 14 weeks, 27 people per group, on top of their usual treatment. Compared with placebo, haemoglobin A1c fell by 0.36 percentage points at 3.0 grams, 0.34 at 3.5 grams and 0.49 at 4.0 grams. Other blood-sugar measures, triglycerides and adiponectin (a hormone from fat tissue linked to better insulin sensitivity) also improved. Mild low blood sugar was more common with salsalate, and the documented episodes occurred only in people also taking sulfonylurea tablets. Urine albumin, a protein whose leakage into urine is a sign of kidney strain, rose in all salsalate groups. The authors wrote that the number of patients and the length of the trial were not enough to support using salsalate for type 2 diabetes, and that its kidney and heart safety needed further study.

Stage 2: one dose for 48 weeks (2013)

286 adults with type 2 diabetes at 21 US centres were randomised to salsalate 3.5 grams a day (146 people) or placebo (140) for 48 weeks, on top of their usual treatment. Over the 48 weeks, average haemoglobin A1c was 0.37 percentage points lower with salsalate (95% confidence interval 0.21 to 0.53 lower). Blood sugar improved even though the salsalate group had more of their other diabetes medicines reduced. White blood cell counts fell, a sign of the anti-inflammatory effect. Fasting glucose, uric acid and triglycerides fell; adiponectin and haematocrit rose.

The trial also recorded effects in the other direction. Body weight and low-density lipoprotein cholesterol (the cholesterol carried in the particles linked to artery disease) increased with salsalate. Urine albumin rose, though it returned to baseline after the drug was stopped, and estimated kidney filtration rate did not change. The authors described these as "mixed cardiorenal signals" and stated that the trial was too short and too small to judge long-term benefit against risk.

The blood-vessel side study (TINSAL-FMD, 2013)

A side study within TINSAL-T2D enrolled 88 people, with data for 75, and measured flow-mediated dilation, an ultrasound test of how well the arm artery widens, a marker of blood-vessel lining health. Over 6 months of salsalate 3.5 grams a day against placebo, haemoglobin A1c fell by 0.46 percentage points, fasting glucose by 16.1 milligrams per decilitre and white cell count by 430 cells per microlitre. Artery widening did not change. Total and low-density lipoprotein cholesterol were 11 and 16 milligrams per decilitre higher with salsalate, and urine albumin was 2.0 micrograms per milligram of creatinine higher. The authors offered three possible explanations: salsalate may not affect inflammation in the vessel wall, inflammation may not be what damages vessels in type 2 diabetes, or other effects of salsalate may cancel out a benefit.

Across these trials the blood-sugar effect was roughly a third to a half of a percentage point of haemoglobin A1c. The Type 2 Diabetes page covers the condition and its treatments.

Prediabetes and Insulin Resistance Studies

Smaller trials tested salsalate in people who did not yet have diabetes:

• Obese young adults (2008). In a one-month trial in 20 obese adults without diabetes, salsalate lowered fasting glucose by 13%, the glucose rise after a sugar drink by 20% and glycated albumin (a shorter-term blood-sugar marker) by 17%, compared with placebo. Adiponectin rose 57%. C-reactive protein, an inflammation marker, fell 34% within the salsalate group.
• Impaired fasting glucose or glucose tolerance (2013). In a 12-week trial in 71 people with prediabetes from two Veterans Affairs health systems, salsalate (up to 4 grams a day) did not change how fast the body cleared glucose under insulin, the main measure. Fasting glucose fell 6% with salsalate, triglycerides were 25% lower and adiponectin 53% higher by the end. Insulin was cleared from the blood more slowly. Blood pressure, artery function and other inflammation markers did not differ. Tinnitus was infrequent but more common with salsalate (4 people against 2). The authors concluded that the glucose fall was not explained by better insulin sensitivity in the body's tissues, which points to other mechanisms, including slower insulin clearance.
• Insulin-resistant adults without diabetes, cholesterol detail (2015). A 4-week study gave salsalate 3.5 grams a day to 27 people and placebo to 14. Directly measured low-density lipoprotein cholesterol did not change. Triglycerides and very-low-density lipoprotein cholesterol fell, and low-density particles shifted from small, dense ones toward larger ones. The authors described this as a less atherogenic pattern whose clinical importance is unknown. This short result differs from the cholesterol rise recorded in the longer TINSAL trials.
• Heart patients without diabetes (2017). Among 192 people without diabetes in the 30-month TINSAL-CVD heart trial (next section), salsalate lowered fasting glucose by 5.70 milligrams per decilitre and haemoglobin A1c by 0.11 percentage points compared with placebo. Urine albumin rose by 16.7 micrograms per milligram. The authors wrote that salsalate might lower the risk of developing type 2 diabetes but that "renal safety may limit clinical utility."

No trial has tested whether salsalate prevents people from developing diabetes. The Insulin Resistance page covers the condition itself.

Heart and Blood Vessel Findings

Because inflammation is part of artery disease, researchers asked whether salsalate could slow it. The results were neutral or unfavourable:

• TINSAL-CVD (2016). 257 overweight or obese people with stable coronary heart disease, all taking a statin, were randomised to salsalate 3.5 grams a day or placebo for 30 months. The main measure was growth of non-calcified (soft) plaque in the heart arteries, measured by CT angiography. There was no difference between groups (mean difference 1 cubic millimetre less with salsalate, 95% confidence interval 11 less to 9 more). The placebo group's plaque did not grow either, which the authors noted limits what the trial can show. Salsalate lowered white cell counts and raised adiponectin, without changing C-reactive protein. Fasting glucose, triglycerides, uric acid and bilirubin fell; haemoglobin rose. Urine albumin rose, and tinnitus and atrial arrhythmias (irregular rhythms of the upper heart chambers) were more common with salsalate.
• Artery widening in a broad group (2014). A crossover trial gave 4 weeks of high-dose salsalate and 4 weeks of placebo to 58 people: 17 with metabolic syndrome, 13 with artery disease and 28 healthy volunteers. Flow-mediated dilation was worse after salsalate than after placebo, and the impairment was seen in people whose blood salicylate reached the therapeutic range. The authors wrote that the findings "raise concern about the possible deleterious effects of anti-inflammatory doses of salsalate on cardiovascular risk."
• TINSAL-FMD (2013). As described above, artery widening in people with type 2 diabetes did not change over 6 months.

The label also carries the class warning that non-steroidal anti-inflammatory drugs may increase the risk of heart attack and stroke, and that the drug is contraindicated for pain around coronary artery bypass surgery.

Tau, Alzheimer's Disease and Progressive Supranuclear Palsy

Tau is a protein that builds up in the brain in Alzheimer's disease and related conditions called tauopathies. A 2015 study found that tau carrying an acetyl mark at one particular site is an early change in Alzheimer's brains and slows the clearance of tau in mice. The enzyme that adds this mark, called p300, was blocked by salsalate and salicylate. In mice bred to develop a tauopathy, salsalate given after the disease had begun lowered total and acetylated tau, reversed tau-related memory problems and prevented shrinkage of the hippocampus, the brain's memory centre. These were mouse results.

The first human report came from progressive supranuclear palsy, a tauopathy that affects balance, eye movement and thinking. In a 2020 open-label study, 10 people with the classic form took salsalate 2,250 milligrams a day for 6 months. The drug was safe and well tolerated, but disease progression on the standard rating scale (an increase of 5.6 points) matched that of historical patients who did not receive it (also 5.6 points), and midbrain shrinkage did not differ either. The authors concluded that salsalate had no detectable effect on progression. The study was small, unblinded and had no randomised control group. No published controlled trial of salsalate in Alzheimer's disease was found for this page.

Side Effects Seen in the Trials

Across the studies above, the same effects recurred:

• Tinnitus and hearing loss. Ringing in the ears is the classic sign of high salicylate levels. It led most withdrawals from salsalate in the diclofenac and naproxen comparisons and was more common with salsalate in the prediabetes and TINSAL-CVD trials. The label lists tinnitus, nausea, hearing impairment, rash and vertigo as the most common reactions in two controlled trials, and states that tinnitus or reversible hearing impairment is often used as a guide to dosing. The Tinnitus page covers other causes.
• More albumin in the urine. Seen in every TINSAL trial. In the 48-week trial it reversed after stopping and kidney filtration did not change, but its long-term meaning is not known.
• Higher low-density lipoprotein cholesterol. Recorded in the 48-week TINSAL-T2D trial and the TINSAL-FMD side study, though not in a 4-week study that measured it directly.
• Weight gain. Recorded in the 48-week TINSAL-T2D trial.
• Low blood sugar. Mild episodes, documented only in people also taking sulfonylureas, in the 14-week trial.
• Atrial arrhythmias. More common with salsalate in TINSAL-CVD.

Spontaneous reports listed on the label, without an established cause-and-effect link, include abdominal pain, abnormal liver tests, hepatitis, anaphylactic shock, angioedema (swelling of the face and throat), bronchospasm, reduced kidney clearance, nephritis, gastrointestinal bleeding, low blood pressure and hives.

Label Warnings and Interactions

Salicylate toxicity

The label states that toxic effects are not usually seen until blood salicylic acid exceeds 30 milligrams per 100 millilitres, the top of the target range. It also states that a sudden fall in urine pH, for example from 6.5 to 5.5, can double the blood level, and that aspirin and other salicylates add to salsalate and can push salicylic acid to toxic levels. The label lists the usual signs of salicylism as tinnitus, vertigo, headache, confusion, drowsiness, sweating, fast breathing, vomiting and diarrhoea, with severe poisoning upsetting the body's salt and acid balance and causing high temperature and dehydration. It states that death has followed ingestion of 10 to 30 grams of salicylates in adults. Hospitals treat salicylate poisoning as an emergency; severe cases may need dialysis.

Reye syndrome

Reye syndrome is a rare, serious illness of the liver and brain, mostly in children and teenagers recovering from a viral infection. The label states that some studies suggest a possible link between Reye syndrome and medicines containing salicylate or aspirin, and on that basis advises against salsalate in people with chickenpox, influenza or flu symptoms. It states that safety and effectiveness in children have not been established.

Asthma and aspirin sensitivity

Salsalate is contraindicated in people who have had asthma, hives or allergic-type reactions after aspirin or other anti-inflammatory drugs. In a 1990 challenge study of 10 people with aspirin-sensitive asthma, all 10 reacted to aspirin, while 2 reacted to 2 grams of salsalate; those reactions were mild and settled with inhaled reliever medicine. The authors concluded that salsalate is less likely than aspirin to trigger asthma in these patients but can occasionally cross-react.

Kidneys, stomach, heart, liver and pregnancy

• The label states that long-term use of drugs in this class has caused kidney damage, that people with kidney disease, heart failure, liver disease, older adults and those on diuretics or ACE inhibitors are at greatest risk, and that there is no controlled information in advanced kidney disease, where the label advises against use.
• The class warnings on stomach bleeding and on heart attack and stroke apply, as described above, as do warnings on new or worse high blood pressure, fluid retention, liver injury and serious skin reactions.
• For pregnancy, the label states that drugs of this class, including salsalate, at about 30 weeks or later can close a vital fetal blood vessel (the ductus arteriosus) too early, and that use from about 20 weeks can reduce fetal kidney function and amniotic fluid. Salicylic acid passes into breast milk at concentrations close to the mother's blood level.

Interactions named on the label

• Anticoagulants. The label states that salicylates taken with anticoagulant drugs may predispose to bleeding throughout the body, and that warfarin and drugs of this class together raise the risk of serious gastrointestinal bleeding more than either alone. Salicylate also competes with warfarin for binding to blood proteins.
• Methotrexate. The label states that drugs of this class may increase methotrexate toxicity, and that salicylate competes with methotrexate for protein binding.
• Other salicylates, including aspirin. Additive, with a risk of toxic levels.
• Sulfonylurea diabetes tablets. Salicylates may strengthen their blood-sugar-lowering effect.
• Gout medicines. Salicylates block the action of drugs that help the kidneys clear uric acid.
• Blood pressure medicines and diuretics. The effect of ACE inhibitors, furosemide and thiazides may be reduced.
• Lithium. Drugs of this class raised lowest blood lithium levels by 15% and cut its kidney clearance by about 20%.
• Thyroid tests. Salicylate can lower the measured T4 thyroid hormone level without changing thyroid function.

Decisions about this medicine and the others it interacts with belong with a prescriber.

What Is Not Known

• Whether salsalate's lower stomach damage on endoscopy translates into fewer serious bleeds and hospital admissions over years; the comparative studies were small and lasted days to months.
• Whether the blood-sugar benefit lasts beyond the longest trials (48 weeks in diabetes, 30 months in people without diabetes), and whether it reduces diabetes complications, heart attacks or deaths. No such outcome trial exists.
• What the rise in urine albumin and in low-density lipoprotein cholesterol means for the kidneys and heart over the long term. The trial authors themselves named kidney safety as a likely limit on use.
• Exactly how salsalate lowers blood sugar. The prediabetes trial found no gain in tissue insulin sensitivity, with slower insulin clearance and lower inflammation both proposed.
• Whether the tau-lowering effect seen in mice occurs in people. The one small human study in progressive supranuclear palsy found no effect on progression.
• How the current tablets would fare in a formal FDA approval review, since they are listed as marketed without an approved application.

Key Research Papers

1. Dromgoole SH, Cassell S, Furst DE, Paulus HE. Availability of salicylate from salsalate and aspirin. Clin Pharmacol Ther. 1983;34(4):539-45. PubMed PMID: 6617077
2. Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis? The Multicenter Salsalate/Aspirin Comparison Study Group. J Rheumatol. 1989;16(3):321-7. PubMed PMID: 2657048
3. Cryer B, Goldschmiedt M, Redfern JS, Feldman M. Comparison of salsalate and aspirin on mucosal injury and gastroduodenal mucosal prostaglandins. Gastroenterology. 1990;99(6):1616-21. PubMed PMID: 2227277
4. Roth S, Bennett R, Caldron P, Hartman R, Mitchell C, Doucette M, et al. Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study. Semin Arthritis Rheum. 1990;19(4 Suppl 2):11-9. PubMed PMID: 2181673
5. Stevenson DD, Hougham AJ, Schrank PJ, Goldlust MB, Wilson RR. Salsalate cross-sensitivity in aspirin-sensitive patients with asthma. J Allergy Clin Immunol. 1990;86(5):749-58. PubMed PMID: 2229840
6. Sweeney JD, Hoernig LA. Hemostatic effects of salsalate in normal subjects and patients with hemophilia A. Thromb Res. 1991;61(1):23-7. PubMed PMID: 2020937
7. Bombardier C, Peloso PM, Goldsmith CH. Salsalate, a nonacetylated salicylate, is as efficacious as diclofenac in patients with rheumatoid arthritis. Salsalate-Diclofenac Study Group. J Rheumatol. 1995;22(4):617-24. PubMed PMID: 7791151
8. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care. 2008;31(2):289-94. PubMed PMID: 17959861
9. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2010;152(6):346-57. PubMed PMID: 20231565
10. Rumore MM, Kim KS. Potential role of salicylates in type 2 diabetes. Ann Pharmacother. 2010;44(7-8):1207-21. PubMed PMID: 20516365
11. Goldfine AB, Conlin PR, Halperin F, Koska J, Permana P, Schwenke D, et al. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance. Diabetologia. 2013;56(4):714-23. PubMed PMID: 23370525
12. Goldfine AB, Fonseca V, Jablonski KA, Chen YD, Tipton L, Staten MA, et al. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann Intern Med. 2013;159(1):1-12. PubMed PMID: 23817699
13. Goldfine AB, Buck JS, Desouza C, Fonseca V, Chen YD, Shoelson SE, et al. Targeting inflammation using salsalate in patients with type 2 diabetes: effects on flow-mediated dilation (TINSAL-FMD). Diabetes Care. 2013;36(12):4132-9. PubMed PMID: 24130358
14. Nohria A, Kinlay S, Buck JS, Redline W, Copeland-Halperin R, Kim S, et al. The effect of salsalate therapy on endothelial function in a broad range of subjects. J Am Heart Assoc. 2014;3(1):e000609. PubMed PMID: 24390146
15. Ariel D, Kim SH, Liu A, Abbasi F, Lamendola CA, Grove K, et al. Salsalate-induced changes in lipid, lipoprotein, and apoprotein concentrations in overweight or obese, insulin-resistant, nondiabetic individuals. J Clin Lipidol. 2015;9(5):658-63. PubMed PMID: 26350812
16. Min SW, Chen X, Tracy TE, Li Y, Zhou Y, Wang C, et al. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med. 2015;21(10):1154-62. PubMed PMID: 26390242
17. Hauser TH, Salastekar N, Schaefer EJ, Desai T, Goldfine HL, Fowler KM, et al. Effect of Targeting Inflammation With Salsalate: The TINSAL-CVD Randomized Clinical Trial on Progression of Coronary Plaque in Overweight and Obese Patients Using Statins. JAMA Cardiol. 2016;1(4):413-23. PubMed PMID: 27438317
18. Salastekar N, Desai T, Hauser T, Schaefer EJ, Fowler K, Joseph S, et al. Salsalate improves glycaemia in overweight persons with diabetes risk factors of stable statin-treated cardiovascular disease: A 30-month randomized placebo-controlled trial. Diabetes Obes Metab. 2017;19(10):1458-1462. PubMed PMID: 28295931
19. VandeVrede L, Dale ML, Fields S, Frank M, Hare E, Heuer HW, et al. Open-Label Phase 1 Futility Studies of Salsalate and Young Plasma in Progressive Supranuclear Palsy. Mov Disord Clin Pract. 2020;7(4):440-447. PubMed PMID: 32373661

Other Sources

1. DailyMed, National Library of Medicine. Salsalate tablets, USP 500 mg and 750 mg: prescribing information and NSAID medication guide (label revised 08-2022; marketing category "unapproved drug other"). DailyMed label

PubMed Topic Searches

1. salsalate type 2 diabetes randomized
2. salsalate rheumatoid arthritis
3. nonacetylated salicylate gastrointestinal
4. salsalate tau

Connections

• Drugs — every drug page on the site
• Aspirin — the acetylated salicylate, its history and its platelet effect
• Meadowsweet Benefits — a herb whose natural salicylates are also non-acetylated
• Willow Bark, Meadowsweet and the Natural Salicylates Behind Aspirin — where salicylate medicines came from
• Rheumatoid Arthritis — salsalate's main labelled use
• Osteoarthritis — the other labelled use
• Type 2 Diabetes — the condition studied in the TINSAL-T2D trials
• Insulin Resistance — the target of the prediabetes studies
• Tinnitus — the most common salicylate side effect

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