The drug that treats both Type 1 and Type 2 diabetes — but through fundamentally different mechanisms — is sotagliflozin, marketed as Inpefa. Approved by the FDA in May 2023, sotagliflozin is the first and only dual SGLT1/SGLT2 inhibitor, meaning it works in two places at once: it blocks glucose absorption in the gut (via SGLT1) and prevents glucose reabsorption in the kidneys (via SGLT2). What makes it genuinely unusual is that it was clinically tested in both Type 1 and Type 2 diabetes populations, showing measurable benefits in each — but the FDA only granted approval for Type 2 diabetes-related cardiovascular outcomes. The rejection for Type 1 use, which came in 2019, hinged on a significantly elevated risk of diabetic ketoacidosis, a potentially life-threatening complication. This distinction matters for anyone tracking the intersection of metabolic disease and brain health.
Diabetes is one of the most well-established modifiable risk factors for dementia, and how blood sugar is managed — or mismanaged — across both types has direct implications for long-term cognitive outcomes. The fact that a single molecule can act on both forms of diabetes, yet carries different risk profiles depending on which type a patient has, raises important questions about personalized treatment and the limits of one-size-fits-all drug approval. Beyond sotagliflozin, two other drugs are reshaping the diabetes treatment landscape in ways that blur the old boundary between Type 1 and Type 2. Tirzepatide, the dual GLP-1/GIP agonist sold as Mounjaro and Zepbound, is increasingly used off-label in Type 1 diabetes at lower doses than in Type 2, with formal clinical guidance expected in June 2026. And teplizumab (Tzield), approved in November 2022 as the first drug ever to delay the onset of Type 1 diabetes, represents a completely different approach — one rooted in immune modulation rather than glucose handling. This article examines all three drugs, what they mean for patients living with either form of diabetes, and why the distinction between the two types is becoming more medically nuanced than ever.
Table of Contents
- How Does Sotagliflozin Treat Type 1 and Type 2 Diabetes Differently?
- Why the FDA Said Yes for Type 2 and No for Type 1
- Tirzepatide — The Off-Label Crossover Drug Gaining Ground in Type 1
- Teplizumab — A Different Strategy That Only Works for One Type
- The DKA Risk — What Every Patient and Caregiver Should Know
- Diabetes as a Dementia Risk Factor — Why These Drugs Matter Beyond Blood Sugar
- What to Watch in 2026 and Beyond
- Conclusion
- Frequently Asked Questions
How Does Sotagliflozin Treat Type 1 and Type 2 Diabetes Differently?
The core of sotagliflozin’s dual action comes down to anatomy. By inhibiting SGLT2 in the kidneys, the drug causes excess glucose to be excreted in urine — a mechanism shared with other SGLT2 inhibitors like empagliflozin and dapagliflozin. But sotagliflozin also inhibits SGLT1 in the small intestine, which reduces how much glucose and sodium the gut absorbs after a meal. In a Type 2 diabetes patient, whose body still produces insulin but uses it inefficiently, this double mechanism helps reduce post-meal glucose spikes and supports cardiovascular health. The FDA approval was based on 11,806 total participants across the SOLOIST-WHF and SCORED phase 3 trials, conducted at 1,072 sites in 42 countries. In the SOLOIST trial alone, involving 1,222 patients, sotagliflozin reduced cardiovascular deaths and hospitalizations or urgent visits for heart failure by 33% compared to placebo after just nine months. In Type 1 diabetes, the picture looks different.
Because Type 1 patients produce little or no insulin due to autoimmune destruction of beta cells, they rely entirely on exogenous insulin. When sotagliflozin was added to insulin in the inTandem clinical trials, it reduced HbA1c by 0.36% at the 200 mg dose and 0.41% at the 400 mg dose over 24 weeks. Some 40.3% of patients on the 400 mg dose achieved an A1C below 7.0%, compared to just 15.7% on placebo. Perhaps more meaningfully for daily life, the drug also reduced severe hypoglycemia from 9.7% in the placebo group to 6.5%. However, the benefit came with a significant safety tradeoff. Diabetic ketoacidosis events in the Type 1 trials occurred at a rate of 3.1 to 4.2 events per 100 patient-years with sotagliflozin, compared to just 0.2 per 100 patient-years with placebo — a roughly 15- to 20-fold increase. DKA is dangerous in any patient, but in Type 1 diabetes, where insulin levels can drop suddenly and unpredictably, the risk was deemed too high by the FDA. This is not a theoretical concern: DKA can cause cerebral edema, particularly in younger patients, and recurrent episodes are associated with cognitive decline — a fact that makes the FDA’s caution especially relevant for those of us focused on long-term brain health.
Why the FDA Said Yes for Type 2 and No for Type 1
The FDA’s split decision on sotagliflozin was not about whether the drug worked in Type 1 diabetes — it clearly did, based on the inTandem data. The rejection in 2019 was a risk-benefit calculation. In Type 2 diabetes, the cardiovascular benefits were substantial and the DKA risk was manageable because these patients still produce some endogenous insulin. Their metabolic baseline is more stable, and ketone production is less likely to spiral out of control. The current approved indication reflects this: sotagliflozin is indicated for reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or Type 2 diabetes with chronic kidney disease and other cardiovascular risk factors. Notably, it is not approved specifically for glycemic control, even in Type 2.
For Type 1 patients, the DKA problem was not something that could easily be engineered away with dose adjustments or monitoring protocols — at least not to the FDA’s satisfaction. Lexicon Pharmaceuticals, the drug’s developer, had partnered with Sanofi to pursue the Type 1 indication, but the regulatory path closed after the 2019 rejection. This does not mean sotagliflozin is never used in Type 1 patients. Off-label use occurs, particularly in countries where regulatory frameworks differ, and some endocrinologists in the United States prescribe it selectively with close monitoring. However, if you or a family member has Type 1 diabetes and is considering this medication, the critical thing to understand is that the DKA risk is real and requires active management — frequent ketone monitoring, clear sick-day protocols, and a provider who understands the specific pharmacology involved. Without those safeguards, the brain health benefits of better glucose control could be negated by the neurological damage a severe DKA episode can cause.
Tirzepatide — The Off-Label Crossover Drug Gaining Ground in Type 1
While sotagliflozin was designed from the start to work across both diabetes types, tirzepatide’s crossover into Type 1 diabetes is happening more organically — driven by clinical observation and a growing body of research. Tirzepatide, sold as Mounjaro for Type 2 diabetes and Zepbound for obesity, is a dual GLP-1/GIP receptor agonist. It was FDA-approved for Type 2 diabetes and has become one of the most talked-about medications in endocrinology, largely because of its dramatic effects on weight loss and blood sugar control. But it was never tested or approved for Type 1 diabetes — until clinicians and researchers started noticing that many Type 1 patients also carry excess weight and could benefit from the same metabolic pathways. The data that has emerged is striking. In a one-year study of tirzepatide in Type 1 patients with obesity, participants achieved an average weight loss of 18.5%, which translates to more than 46 pounds. HbA1c decreased by 0.67% from a baseline of 7.7%, with improvements holding steady from three months onward. A six-month study showed a mean 9.3% weight reduction and an HbA1c drop from 7.7% to 7.4%.
Researchers at EASD in 2025 reported average weight loss of approximately 20 pounds over just 12 weeks. Beyond the numbers, tirzepatide also improved time in range — the percentage of the day a patient’s blood sugar stays within target — along with cardiovascular and kidney disease risk factors. One key difference in how tirzepatide is used across the two diabetes types is dosing. In Type 2 diabetes, doses can go as high as 15 mg weekly. In Type 1 patients, most achieve meaningful benefits at 7.5 to 10 mg weekly, and these lower doses are better tolerated. This matters because higher doses are associated with more gastrointestinal side effects — nausea, vomiting, reduced appetite — that can be particularly problematic for Type 1 patients who must carefully calibrate insulin doses around food intake. new consensus guidance titled “Adjunctive Treatment with GLP/GIPs for Patients with T1D” is expected in June 2026, which will be the first formal clinical framework for this off-label use. Until then, patients and providers are navigating largely without a map.
Teplizumab — A Different Strategy That Only Works for One Type
Not every drug that matters in this conversation treats both types of diabetes. Teplizumab, marketed as Tzield, was approved by the FDA in November 2022 as the first drug ever to delay the onset of clinical Type 1 diabetes. It works by a completely different mechanism than either sotagliflozin or tirzepatide: rather than managing glucose after diabetes has developed, teplizumab modulates the immune system to slow down the autoimmune attack that destroys insulin-producing beta cells in the pancreas. Specifically, it is an anti-CD3 monoclonal antibody that targets the T lymphocytes responsible for that destruction. The drug is approved for adults and children aged eight and older who have Stage 2 Type 1 diabetes — meaning they have two or more diabetes-related autoantibodies and abnormal glucose tolerance, but have not yet progressed to clinical diagnosis. According to data from the TrialNet research network, teplizumab delays the diagnosis of full-blown Type 1 diabetes by a median of two years.
That may sound modest, but for a child or young adult facing a lifetime of insulin dependence, two additional years of functional beta cell mass can mean two more years of easier blood sugar management, fewer hypoglycemic episodes, and potentially reduced risk of the vascular complications that contribute to cognitive decline later in life. The tradeoff is that teplizumab has no application whatsoever in Type 2 diabetes. Type 2 is not an autoimmune disease — the beta cells are still present, though they may be dysfunctional or overwhelmed. Immunomodulation does nothing to address insulin resistance or the metabolic syndrome that drives Type 2. This distinction is worth understanding clearly, because as more drugs cross the Type 1/Type 2 boundary, teplizumab stands as a reminder that the two diseases, despite sharing a name, have fundamentally different origins. For families with a history of autoimmune conditions and a young person showing early markers, teplizumab represents something that did not exist three years ago: the ability to buy time.
The DKA Risk — What Every Patient and Caregiver Should Know
Diabetic ketoacidosis deserves its own section because it is the central reason the most promising dual-diabetes drug carries a warning label for half its potential patient population. DKA occurs when the body, starved for insulin, begins breaking down fat for energy and producing ketones at a dangerous rate. Blood becomes acidic, and without rapid treatment, DKA can cause organ damage, coma, and death. In the context of brain health specifically, DKA episodes are associated with acute cerebral edema and, over time, cumulative cognitive impairment. In the sotagliflozin Type 1 trials, DKA rates of 3.1 to 4.2 events per 100 patient-years were not just statistically significant — they represented a qualitative shift in risk.
For comparison, the background rate in the placebo group was 0.2 per 100 patient-years. The mechanism is somewhat paradoxical: SGLT2 inhibitors lower blood glucose so effectively that patients or providers may reduce insulin doses, which in turn creates the conditions for ketone buildup even when blood sugar readings look acceptable. This is sometimes called euglycemic DKA, and it is particularly dangerous precisely because the usual warning sign — high blood sugar — is absent. For anyone with Type 1 diabetes considering an SGLT inhibitor, or for caregivers managing someone with both diabetes and cognitive impairment, this is not a risk to dismiss casually. Patients with dementia or early cognitive decline may not recognize or communicate the symptoms of DKA — nausea, confusion, rapid breathing — and those symptoms can easily be mistaken for progression of the neurological condition rather than a metabolic emergency. Any off-label use of sotagliflozin in Type 1 diabetes requires robust ketone monitoring, ideally with a continuous ketone monitor if available, and a care team that understands the specific risks at the intersection of metabolic and cognitive disease.
Diabetes as a Dementia Risk Factor — Why These Drugs Matter Beyond Blood Sugar
The reason a brain health publication is covering diabetes drugs is straightforward: diabetes is one of the strongest modifiable risk factors for Alzheimer’s disease and vascular dementia. Type 2 diabetes approximately doubles the risk of dementia, and Type 1 diabetes — particularly when complicated by recurrent hypoglycemia or DKA episodes — carries its own set of cognitive risks. Drugs that improve glycemic stability, reduce cardiovascular events, or protect kidney function are not just diabetes treatments; they are, potentially, neuroprotective interventions.
Sotagliflozin’s 33% reduction in cardiovascular death and heart failure hospitalization is relevant here because heart failure and cerebrovascular disease share overlapping pathophysiology. Tirzepatide’s improvements in time-in-range and cardiovascular risk factors in Type 1 patients address another pathway to cognitive decline. And teplizumab’s ability to delay Type 1 onset by two years means two fewer years of the glycemic variability that damages small blood vessels in the brain. None of these drugs were developed with dementia prevention as their primary goal, but the downstream effects on brain health may turn out to be among their most important contributions.
What to Watch in 2026 and Beyond
The biggest development on the immediate horizon is the expected publication in June 2026 of formal consensus guidance on using GLP-1/GIP receptor agonists like tirzepatide as adjunctive therapy in Type 1 diabetes. This guidance, titled “Adjunctive Treatment with GLP/GIPs for Patients with T1D,” will be the first structured clinical framework for what is currently off-label practice. If the guidance supports tirzepatide use at lower doses — as the emerging data suggests it should — it will effectively create a new standard of care for the substantial population of Type 1 patients who also struggle with obesity and its associated cardiovascular risks.
Meanwhile, Lexicon Pharmaceuticals and other companies continue to study SGLT inhibitors in various patient populations, and the question of whether sotagliflozin or similar drugs could safely be used in Type 1 diabetes with adequate monitoring protocols remains open. The broader trend is unmistakable: the hard line between Type 1 and Type 2 diabetes treatments is dissolving, replaced by a more nuanced approach that considers each patient’s full metabolic and cardiovascular profile. For those of us who think about brain health, this evolution is worth tracking closely — because every improvement in how diabetes is managed is, in some measure, an improvement in how we protect the aging brain.
Conclusion
Sotagliflozin remains the most literal answer to the question of which drug treats both Type 1 and Type 2 diabetes differently. Its dual SGLT1/SGLT2 mechanism demonstrated clear benefits in both patient populations across rigorous clinical trials, but the DKA risk in Type 1 patients led the FDA to approve it only for Type 2 diabetes-related cardiovascular outcomes. Tirzepatide is the emerging story, with off-label use in Type 1 growing and formal guidance on the way.
Teplizumab, though exclusive to Type 1, represents a paradigm shift in how we think about preventing diabetes rather than just treating it. For patients, caregivers, and anyone concerned about the long-term cognitive consequences of poorly managed diabetes, the practical takeaway is this: talk to your endocrinologist about whether these newer options are relevant to your specific situation. Do not start or stop medications based on headlines — the DKA risks are real, the dosing differences between Type 1 and Type 2 matter, and the monitoring requirements are non-trivial. But the trajectory of treatment is moving in the right direction, toward drugs that are more targeted, more effective, and better matched to the complexity of the diseases they aim to treat.
Frequently Asked Questions
Is sotagliflozin (Inpefa) approved for treating Type 1 diabetes?
No. The FDA rejected sotagliflozin for Type 1 diabetes in 2019 due to elevated rates of diabetic ketoacidosis. It is currently approved only for reducing cardiovascular risk in adults with heart failure or Type 2 diabetes with chronic kidney disease and other cardiovascular risk factors. Some physicians prescribe it off-label for Type 1 with close monitoring, but this is not standard practice.
Can tirzepatide (Mounjaro) be used for Type 1 diabetes?
Tirzepatide is not FDA-approved for Type 1 diabetes, but it is increasingly used off-label, typically at lower doses of 7.5 to 10 mg weekly compared to the 15 mg maximum used in Type 2. Clinical studies have shown significant weight loss and modest HbA1c improvement in Type 1 patients with obesity. Formal consensus guidance on this use is expected in June 2026.
What is the connection between diabetes medications and dementia risk?
Diabetes is one of the strongest modifiable risk factors for dementia. Drugs that improve glycemic stability, reduce cardiovascular events, or protect kidney function may have downstream neuroprotective effects. Both sotagliflozin’s cardiovascular risk reduction and tirzepatide’s improvements in time-in-range could contribute to long-term brain health, though neither drug has been specifically studied for dementia prevention.
What is teplizumab (Tzield) and who is it for?
Teplizumab is the first FDA-approved drug to delay the onset of clinical Type 1 diabetes. Approved in November 2022, it works by modulating the T lymphocytes that destroy insulin-producing beta cells. It is for adults and children aged eight and older with Stage 2 Type 1 diabetes and delays clinical diagnosis by a median of two years. It has no application in Type 2 diabetes.
Why is euglycemic DKA particularly dangerous?
Euglycemic DKA occurs when ketone levels become dangerously elevated while blood sugar remains relatively normal. This is especially dangerous because the usual warning sign — very high blood sugar — is absent. SGLT2 inhibitors like sotagliflozin can contribute to this by lowering glucose effectively enough that insulin doses are reduced, creating conditions for unchecked ketone production. For patients with cognitive impairment, the symptoms of DKA may be mistaken for neurological decline, delaying treatment.
