Diabetes Research Bites: Sulfonylureas & Meals Driving Morning Glucose Spikes

Hello wonderful people and welcome to an episode where we break down the latest science so you can stay ahead of the headlines and noise. In today’s episode, I’ve pulled together some new studies that are worth your attention. We’ll start with a medication that’s been around for decades but is raising fresh concerns, then look at yet another food industry–funded study making big promises about fruit, we chat about medication concerns in youths with diabetes, and finally we’ll end with some new insights into why your evening meal may be the hidden key to your morning fasting glucose.

The first research bite we’re exploring is a concerning one, a medication that’s been around for decades – sulfonylureas. These drugs are still prescribed widely for type 2 diabetes, but new research is painting a concerning picture about their long-term effects, particularly when it comes to heart health and pancreatic beta-cell function.

Let’s look at heart disease risk first. 

A large new study looked at people with type 2 diabetes who were taking metformin and needed a second-line medication. Researchers compared sulfonylureas with DPP-4 inhibitors, another common class of medications.

People on glipizide had about a 13% higher risk of major cardiovascular events – heart attack, stroke, heart failure, or cardiovascular death – compared to those on DPP-4 inhibitors. 13% isn’t 83% risk, but it’s still an increased risk and that’s something you need to know if you’re prescribed these meds. 

Glimepiride showed a smaller increase in risk, while glyburide looked neutral, but the numbers were less precise. The big takeaway is that sulfonylureas, and glipizide in particular, were linked to worse heart outcomes. Considering that heart disease is already the number one cause of death in people with type 2 diabetes, this is a red flag.

Another concern with sulfonylureas that appeared in recent research is concerned on how they work. They essentially force the pancreas to pump out more insulin. That might sound good in theory, but it comes at a cost. 

A new lab study using clusters of insulin-producing beta cells found that chronic exposure to the sulfonylurea glibenclamide triggered some very concerning changes.

The beta cells started leaking insulin at the wrong times, showing impaired glucose-stimulated insulin secretion. There was an increase in beta-cell death.
But most striking, the beta cells lost their identity, meaning they stopped behaving like healthy insulin-producing cells, with reduced expression of key genes. This process was driven in part by endoplasmic reticulum stress inside the cells.

Researchers concluded that sulfonylureas can accelerate the decline of functional beta-cell mass, which helps explain why these drugs so often lose their effectiveness after a few years. 

When you put these two pieces of evidence together, the increased cardiovascular risk and the damage to beta cells, it becomes clear we need to now question whether sulfonylureas should still be a frontline option.

These drugs never made sense to me anyway. It doesn’t make sense to force the pancreas to work harder to push out insulin. We know that type 2 diabetes is fundamentally about insulin resistance, so by forcing more insulin out, sulfonylureas may temporarily lower blood sugar, but they worsen the underlying problem, they worsen the insulin resistance, and potentially accelerate disease progression. And this new evidence suggesting they may cause damage to beta cells is very concerning. 

With our nutrition program, one of the first medications we recommend people come off is sulfolylureas. One of the reasons for that is our programs are so effective and one of the other major side effects of sulfolylureas is they cause hypoglycemia, low blood sugar, and we don’t want people experiencing that either. 

In any case, these two new research bites suggest that sulfonylureas may increase risk for heart disease and cause progressive loss of the very beta cells you need to preserve, so if you are taking these drugs, it may be worthwhile speaking to your medical doctor about deprescribing them. 

Onto our next topic. If you’ve listened to the podcast for a whle, you’ve heard me say not all research is good research and in fact, it’s common to see a lot of bad research making big claims across news headlines. Back in episode 80, we covered some bad research claiming that eating 2 cups of mango a day prevents diabetes. No truth in that of course. The study was poorly designed and the study practically demonstrates nothing. After that stupid study, I’d thought we’d seen the end of that nonsense. Well, apparently not. 

A new trial tested whether eating one mango every day for 24 weeks improved outcomes in people with prediabetes. On the surface, the results look promising: the mango group had slightly lower fasting glucose and insulin resistance compared to a control group eating a granola bar. Again, the headlines practically wrote themselves – “Mango prevents diabetes.” 

But, the study was tiny, only 23 people completed the study. The researchers also didn’t properly account for overall dietary intake, in fact, they didn’t assess that at all, so the very small changes observed in the study could have been due to other dietary changes they participants made and nothing to do with mangoes. Overall, it was a poor study design. 

Another thing I noted on both of these studies was the industry funding, which came from the National Mango Board, the industry body that sells mangoes. That’s a massive conflict of interest. When researchers take funding from industry, of course, there’s always a vested interest to get a positive result. This is why we need to be cautious about food-industry-funded studies. They’re designed to promote a product, not necessarily uncover the truth. In reality, there’s no evidence that eating mango will stop diabetes. I like to highlight these types of studies to show you there are many sensational headlines circling around the Wild West Web and majority of them carry no weight at all, it’s just rubbish.  

In episode 94 we spoke about the rising rates of diabetes in youths. In that podcast I spoke about one clinical trial that tested canagliflozin medications in adolescents and I highlighted one of my major concerns – starting young people on drugs so early. Yes we know youth-onset T2D is aggressive. So of course, guess which industry is quick to jump on this – the pharmaceutical industry. And so more research is emerging. A new trial, called SURPASS-PEDS, tested tirzepatide, you may know it by its brand name Mounjaro, in children as young as 10 years old with type 2 diabetes. The kids in the trial saw a reduction in A1c and weight loss, which like the earlier trial may look good on paper. But let’s talk about what this really means. The study only included 99 kids, followed for less than a year. That’s a tiny group, and nowhere near enough time to understand the long-term consequences of putting a 10-year-old on a powerful incretin drug for potentially decades.

And the concerns are not trivial. GLP-1–based drugs carry warnings about thyroid tumors in animal studies, there are case reports of pancreatitis, risks of severe gastrointestinal motility problems like ileus, and in adults, up to 40% of weight lost is actually lean mass, not fat. Add to that the reality that when people stop taking these drugs, the weight usually comes back. Imagine what that means for a child who might need this medication for life. Well, the reality is we don’t know. So, yes, tirzepatide clearly lowers blood sugar and body weight, even in kids. But the bigger question is: at what cost? We’re talking about developing bodies, muscle and bone growth, long lifespans ahead, and risks we won’t fully understand for decades. To me, this looks like a short-term fix with very big unknowns attached.

This trial highlights an urgent issue, youth diabetes is skyrocketing, and treatment options are limited. But instead of jumping straight to powerful drugs, we need to ask the harder question: why are so many kids developing type 2 diabetes in the first place, and how can we fix the root causes? Should we be treating children pharmacologically when diet, insulin resistance reversal, and other foundational therapies offer long-term benefit and safety? Are we trading short-term control for unknown long-term harm? Because the last thing we should do is turn a generation of children into lifelong drug patients without knowing the long-term consequences. From the perspective of someone trained in nutrition and protective strategies, to me the medication pathway for children is fraught with ethical and safety implications.

If you know a person, a friend, colleague or family member with a child or adolescent facing diabetes, these are important factors you can pass onto them, because education will be key here. We know that overprescribing happens far too much with adults, we really don’t want to see that in children. 

The last research bite I want to share with you today tackles one of the most frustrating issues for people living with prediabetes or type 2 diabetes: morning blood sugar.

You know the story, you finish the day feeling proud of your food choices, maybe you even avoided dessert, and yet you wake up the next morning to see your fasting glucose is higher than you expected. It feels like a mystery because you didn’t eat overnight, so why is it up?  

Well we’re not going into why here, we covered that in episode 38. What we are going to chat about is two new studies that shed further light on the importance of your evening meal when it comes to your morning blood sugar. 

We’ve known for some time that our bodies don’t process food the same way morning, noon, and night. And there’s been evidence to suggest that eating at least two hours before bed and avoiding snacks can help lower those morning numbers. So why is it that the nighttime meal is so important. According to research, in the evening, your internal biological clock actually makes you less sensitive to insulin. That means the same meal, a bowl of rice, pasta or a slice of bread, can cause a bigger spike at dinner than it would at lunch. Not that I recommend those foods for a healthy diabetes dinner but they are common for many people, and as a result we’re seeing higher spikes occurring. 

This new research confirms this difference in the way our bodies process foods in the evening. Scientists found that the size of the glucose spike after your last meal of the day strongly predicts what your fasting number will be the next morning. In other words, if your blood sugar runs higher during the night, it’s very likely you’ll wake up with a higher fasting glucose too.

And there was another really interesting part to this puzzle. Traditionally, fasting glucose is measured by how many hours you’ve gone without food, usually from your evening meal (or snacks if you’re having them) until morning. For example, you had dinner at 6PM, no snacks, and ate breakfast at 8AM, that’s a 12 hour fast. But researchers are now challenging that idea.

They’ve introduced the concept of the Biological Overnight Fast. Instead of starting the clock the minute you stop eating, they say true fasting only begins once your blood sugar has returned to baseline after dinner. Ideally, that should be within two hours, but let’s just say you did eat that carb-rich meal of rice, pasta or bread, then returning to baseline might take three, four, or even more hours depending on what you ate. This concept of the Biological Overnight Fast means your body may not truly be “fasting” until well after you’ve finished eating.

When they measured glucose during this biological fasting window, the average numbers were in the high 80s to low 90s mg/dL (4.4-5.0 mmol/L), which is right in the healthy range. But if your glucose didn’t return to baseline before bed, for example, because of a carb-heavy dinner, overnight levels stayed elevated, and so did the morning reading.

This new research just emphasizes the importance of what you eat at your evening meal.

Carbs are the main nutrient that raise blood sugar, and in the evening your body is naturally less efficient at handling them. That means a carb-heavy dinner or snacking in the evening is much more likely to keep your glucose elevated through the night and show up as a higher reading in the morning. When carbs are limited at dinner, and replaced with a balanced nutrient dense meal with protein, non-starchy vegetables and healthy fats, blood sugar levels will come down to baseline faster so you’re actually reaching true fasting in a timely fashion, ideally 2 hours after your last meal, and blood sugar will stay steadier overnight. That’s the overarching theory behind this strategy so if you’re morning levels are a concern, try focusing on your evening meal. 

If you’re one of our VIP members, we’ve added a detailed action plan around this inside your Lower Fasting Blood Sugar Healthmap, so head to the Guides where you can find that, or you can also find it alongside this episode of the podcast in the members library.  

So that wraps up today’s research bites. First, we saw that sulfonylureas, an old class of diabetes drugs, carry real concerns, not only the potential for increasing cardiovascular risk but also harming the very beta cells you need to preserve. Then we looked at the so-called “mango study,” a perfect example of poor design and industry influence creating headlines that don’t hold up to scrutiny. We spoke about the ethical and safety concerns around medications in youths with diabetes. And finally, the evening meal research reminded us that your dinner choices have a direct impact on those frustrating morning fasting numbers, something you can actually control and act on right away.

The theme across all of this is clear: whether it’s medications, food industry hype, or daily meal patterns, the choices we make and the evidence we follow matter. My goal is to help you separate fact from fiction, so you can focus on what truly supports better blood sugar and long-term health.

That’s all for now. 

Stay focused on what you can do today, that’s where your power lies.

Dr Jedha, over and out.