Japan Study Ranks Basal Insulins for Type 1 Diabetes Safety

A study from Japan offers Type 1 diabetes patients and their doctors a clearer picture of how modern basal insulins stack up against older options — particularly when it comes to the risk of dangerous low blood sugar episodes that can disrupt daily life.

Researchers at Osaka University's Graduate School of Pharmaceutical Sciences conducted a rigorous systematic review and network meta-analysis, pooling data from 18 randomized controlled trials involving 7,283 adults with Type 1 diabetes (T1D). Their goal was to compare second-generation basal insulins — insulin glargine U300 (Toujeo) and insulin degludec U100 (Tresiba) — against older options including NPH insulin and first-generation basal insulins like glargine U100 (Lantus, Basaglar) and detemir (Levemir).

What the Researchers Found

The most reassuring finding: newer insulins worked just as well as older insulins at lowering HbA1c (a 3-month blood sugar average). However, the real differences emerged in safety, not effectiveness.

• Severe hypoglycemia risk: NPH insulin carried a significantly higher risk of patients experiencing severe low blood sugar compared to both second-generation insulins. Severe hypoglycemia — episodes requiring outside assistance — can lead to seizures, loss of consciousness, and emergency room visits.
• Nocturnal (nighttime) hypoglycemia: Both NPH and first-generation insulins were associated with higher rates of nighttime confirmed low blood sugar events compared to the newer insulins. Nighttime lows are particularly dangerous because patients are often unaware they are occurring.
• Weight gain: Glargine U300 was comparable to detemir for weight gain. However, degludec U100 was associated with greater weight gain than detemir — a factor worth discussing with your care team, especially if weight management is a concern.

Understanding the Numbers

While this study reported outcomes in HbA1c percentages (already in US-standard units), blood sugar thresholds for confirmed hypoglycemia in these trials were typically set at 54 mg/dL or below (equivalent to 3.0 mmol/L), and sometimes 70 mg/dL (3.9 mmol/L) — consistent with American Diabetes Association (ADA) definitions of clinically significant and level-1 hypoglycemia.

Why This Matters for US Patients

The ADA's Standards of Care already recommend second-generation basal insulins as preferred options for many T1D patients, citing their lower hypoglycemia risk. This Japanese meta-analysis, drawing on global trial data, reinforces that guidance with moderate-to-high certainty evidence. For US patients, this research matters for several reasons:

• Insurance and cost decisions: Some insurance plans still favor older, cheaper insulins like NPH or glargine U100. This evidence supports conversations with your insurer or doctor about upgrading to newer options if nighttime or severe lows are a problem.
• Choosing between newer insulins: Both Toujeo and Tresiba appear safer than older insulins, but if weight is a concern, Toujeo may have a slight edge over Tresiba based on this data.
• Global validation: Japan has some of the world's most rigorous pharmaceutical research standards. When Japanese researchers confirm findings already seen in Western trials, it strengthens the evidence across diverse populations.

Always consult your endocrinologist or diabetes care team before switching insulin types. Individual factors — including your daily schedule, hypoglycemia awareness, and insurance coverage — all play a role in finding the right basal insulin for you.

Source: Martin, Zhou, Takagi. "Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis." Naunyn-Schmiedeberg's Archives of Pharmacology (2021). PMID: 34319421. DOI: 10.1007/s00210-021-02128-9