Impact of bodyweight loss on type 2 diabetes remission: a systematic review and meta-regression

[Eddy Edson]

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00346-2/abstract

Background​

Bodyweight loss is associated with type 2 diabetes remission; however, the quantitative relationship between the degree of bodyweight loss and the likelihood of remission, after controlling for confounding factors, remains unknown. We aimed to analyse the relationship between the degree of bodyweight loss and diabetes remission after controlling for various confounding factors, and to provide estimates for the effect sizes of these factors on diabetes remission.

Methods​

This systematic review and meta-regression analysis followed Cochrane and PRISMA guidelines to systematically review, synthesise, and report global evidence from randomised controlled trials done in individuals with type 2 diabetes and overweight or obesity. The outcome was the proportion of participants with complete diabetes remission (HbA1c <6·0% [42 mmol/mol] or fasting plasma glucose [FPG] <100 mg/dL [5·6 mmol/L], or both, with no use of glucose-lowering drugs) or partial diabetes remission (HbA1c <6·5% [48 mmol/mol] or FPG <126 mg/dL [7·0 mmol/L], or both, with no use of glucose-lowering drugs) at least 1 year after a bodyweight loss intervention. We searched PubMed, Embase, and trial registries from database inception up to July 30, 2024. Data were extracted from published reports. Meta-analyses and meta-regressions were performed to analyse the data. The study protocol is registered with PROSPERO (CRD42024497878).

Findings​

We identified 22 relevant publications, encompassing 29 outcome measures of complete diabetes remission and 33 outcome measures of partial remission. The pooled mean proportion of participants with complete remission 1 year after the intervention was 0·7% (95% CI 0·1–4·6) in those with bodyweight loss less than 10%, 49·6% (40·4–58·9) in those with bodyweight loss of 20–29%, and 79·1% (68·6–88·1) in those with bodyweight loss of 30% or greater; no studies reported on complete remission with 10–19% bodyweight loss. The pooled mean proportion of participants with partial remission 1 year after the intervention was 5·4% (95% CI 2·9–8·4) in those with bodyweight loss less than 10%, 48·4% (36·1–60·8) in those with 10–19% bodyweight loss, 69·3% (55·8–81·3) in those with bodyweight loss of 20–29%, and 89·5% (80·0–96·6) in those with bodyweight loss of 30% or greater. There was a strong positive association between bodyweight loss and remission. For every 1 percentage point decrease in bodyweight, the probability of reaching complete remission increased by 2·17 percentage points (95% CI 1·94–2·40) and the probability of reaching partial remission increased by 2·74 percentage points (2·48–3·00). No significant or appreciable associations were observed between age, sex, race, diabetes duration, baseline BMI, HbA1c, insulin use, or type of bodyweight loss intervention and remission. Overall, data were derived from randomised controlled trials with a low risk of bias in all quality domains.

Interpretation​

A robust dose–response relationship between bodyweight loss and diabetes remission was observed, independent of age, diabetes duration, HbA1c, BMI, and type of intervention. These findings highlight the crucial role of bodyweight loss in managing type 2 diabetes and reducing the risk of diabetes-related complications.

I would say key points are:

- Definition used for "complete" remission: HbA1c less than 6% = 42 mmol/mol without meds at least 12 month following weight loss intervention. They also have a "partial" remission definition (HbA1c oless than 6.5% = 48 mmol/mol) which corresponds to the more common remission definition in other studies.

- A really clear dose-response profile. The higher the weight loss, the greater the chance of remission.

- Independent of type of diet & intervention: high carb, low carb, low fat, weight loss meds ... Nothing else counts very much versus weight loss.

- Independent of age & diabetes duration. This is a key difference versus the DiRECT messaging.

- Independent of starting BMI. Consistent with ReTUNE (and my experience!)

- The abstract doesn't give any indication of the proportion of people in the studies achieving & sustaining the various weight loss levels but you can be sure that these reduce as the weight loss amount increases, and the number of people actually sustaining 15%+ weight loss at 12 months would generally be small, unless they include people still on GLP-1 and GIP meds (which I assume they don't).

 

[JITR]

... the number of people actually sustaining 15%+ weight loss at 12 months would generally be small ...

That may well be true in general.

Feedback from members of this forum suggests self-motivated individuals can sustain remission for as long as they like, all things equal.

Research required into HCP delivery v individual responsibiity.

 

[Martin.A]

So in clinical terms what does 'complete remission' mean as opposed to 'in remission'? My HbA1c has been below 42 on every test since August 2019, which qualifies me for 'complete remission' according to this piece.

 

[Eddy Edson]

So in clinical terms what does 'complete remission' mean as opposed to 'in remission'? My HbA1c has been below 42 on every test since August 2019, which qualifies me for 'complete remission' according to this piece.

I doubt that it means very much at all, clinically?

 

[Eddy Edson]

That may well be true in general.

Feedback from members of this forum suggests self-motivated individuals can sustain remission for as long as they like, all things equal.

Research required into HCP delivery v individual responsibiity.

"Self-motivated" is such a complex thing, though.

I've been "self-motivated" enough to maintain ~25% weight loss & remission for 6+ years now but I think that the most important part of that was having the right genotype for little behaviour & dietary mods to be effective without needing massive constant exercise of willpower. I think that a large proportion of the people who don't see the same kind of results try a lot harder for a lot longer than I've ever had to - a lot more "self motivated". On the other hand, this doesn't mean that I think agency is useless and that people are condemnded to obesity by their genes. It's complicated!

This is a great, thoughtful thread from today discussing agency vs determinism in this context:

https://twitter.com/x/status/1933586543341678757

 

[everydayupsanddowns]

Really interesting findings @Eddy Edson

Potentially pretty powerfully motivating (for some people) that the chances of remission were found to be largely independent of factors like diabetes duration. But I think care need to be taken that such findings aren’t misused in any kind of shame / blame / self-blame way.

Also interesting to see an official reframing of remission more in line with forum members feelings here (eg the members who say things like, “Well officially they say remission is at 48, buy I prefer to get myself below 42, which is below ‘at risk’ / prediabetes zone…”)

 

[Burylancs]

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00346-2/abstract

Background​

Bodyweight loss is associated with type 2 diabetes remission; however, the quantitative relationship between the degree of bodyweight loss and the likelihood of remission, after controlling for confounding factors, remains unknown. We aimed to analyse the relationship between the degree of bodyweight loss and diabetes remission after controlling for various confounding factors, and to provide estimates for the effect sizes of these factors on diabetes remission.

Methods​

This systematic review and meta-regression analysis followed Cochrane and PRISMA guidelines to systematically review, synthesise, and report global evidence from randomised controlled trials done in individuals with type 2 diabetes and overweight or obesity. The outcome was the proportion of participants with complete diabetes remission (HbA1c <6·0% [42 mmol/mol] or fasting plasma glucose [FPG] <100 mg/dL [5·6 mmol/L], or both, with no use of glucose-lowering drugs) or partial diabetes remission (HbA1c <6·5% [48 mmol/mol] or FPG <126 mg/dL [7·0 mmol/L], or both, with no use of glucose-lowering drugs) at least 1 year after a bodyweight loss intervention. We searched PubMed, Embase, and trial registries from database inception up to July 30, 2024. Data were extracted from published reports. Meta-analyses and meta-regressions were performed to analyse the data. The study protocol is registered with PROSPERO (CRD42024497878).

Findings​

We identified 22 relevant publications, encompassing 29 outcome measures of complete diabetes remission and 33 outcome measures of partial remission. The pooled mean proportion of participants with complete remission 1 year after the intervention was 0·7% (95% CI 0·1–4·6) in those with bodyweight loss less than 10%, 49·6% (40·4–58·9) in those with bodyweight loss of 20–29%, and 79·1% (68·6–88·1) in those with bodyweight loss of 30% or greater; no studies reported on complete remission with 10–19% bodyweight loss. The pooled mean proportion of participants with partial remission 1 year after the intervention was 5·4% (95% CI 2·9–8·4) in those with bodyweight loss less than 10%, 48·4% (36·1–60·8) in those with 10–19% bodyweight loss, 69·3% (55·8–81·3) in those with bodyweight loss of 20–29%, and 89·5% (80·0–96·6) in those with bodyweight loss of 30% or greater. There was a strong positive association between bodyweight loss and remission. For every 1 percentage point decrease in bodyweight, the probability of reaching complete remission increased by 2·17 percentage points (95% CI 1·94–2·40) and the probability of reaching partial remission increased by 2·74 percentage points (2·48–3·00). No significant or appreciable associations were observed between age, sex, race, diabetes duration, baseline BMI, HbA1c, insulin use, or type of bodyweight loss intervention and remission. Overall, data were derived from randomised controlled trials with a low risk of bias in all quality domains.

Interpretation​

A robust dose–response relationship between bodyweight loss and diabetes remission was observed, independent of age, diabetes duration, HbA1c, BMI, and type of intervention. These findings highlight the crucial role of bodyweight loss in managing type 2 diabetes and reducing the risk of diabetes-related complications.
View attachment 35787
I would say key points are:

- Definition used for "complete" remission: HbA1c less than 6% = 42 mmol/mol without meds at least 12 month following weight loss intervention. They also have a "partial" remission definition (HbA1c oless than 6.5% = 48 mmol/mol) which corresponds to the more common remission definition in other studies.

- A really clear dose-response profile. The higher the weight loss, the greater the chance of remission.

- Independent of type of diet & intervention: high carb, low carb, low fat, weight loss meds ... Nothing else counts very much versus weight loss.

- Independent of age & diabetes duration. This is a key difference versus the DiRECT messaging.

- Independent of starting BMI. Consistent with ReTUNE (and my experience!)

- The abstract doesn't give any indication of the proportion of people in the studies achieving & sustaining the various weight loss levels but you can be sure that these reduce as the weight loss amount increases, and the number of people actually sustaining 15%+ weight loss at 12 months would generally be small, unless they include people still on GLP-1 and GIP meds (which I assume they don't).

The probability of partial remission was '48·4% (36·1–60·8) in those with 10–19% bodyweight loss'

Have they reinvented the wheel ? The 1955 research showed that losing 10% of body weight led to significant improvement on diabetic control. And that figure of 10% has been repeated ad nauseam for the last 70 years in every bit of advice on Type 2.

The figures suggest a Type 2 would need to lose 19% of bodyweight to be in 'partial remission' and 24% to be in 'complete remission'. Both seem like a hard sell and only 5.4% of participants were in 'remission' after a year. That figure of 5.4% suggests the number of participants actually losing 19 and 24% of bodyweight was vanishingly small. Heh, heh, more research needed, the DiRECT study showed that sudden dramatic weight loss is not the way to go for the vast majority of T2s. Type 2s are back being the tortoise in a hare and tortoise race.

 

[JITR]

@Burylancs
Were you advised to lose weight when you were diagnosed? I wasn't in 2022, only to take Metformin.

 

[Eddy Edson]

The figures suggest a Type 2 would need to lose 19% of bodyweight to be in 'partial remission' and 24% to be in 'complete remission'. Both seem like a hard sell and only 5.4% of participants were in 'remission' after a year. That figure of 5.4% suggests the number of participants actually losing 19 and 24% of bodyweight was vanishingly small. Heh, heh, more research needed, the DiRECT study showed that sudden dramatic weight loss is not the way to go for the vast majority of T2s. Type 2s are back being the tortoise in a hare and tortoise race.

Where do those figures come from?

 

[Martin.A]

Also interesting to see an official reframing of remission more in line with forum members feelings here (eg the members who say things like, “Well officially they say remission is at 48, buy I prefer to get myself below 42, which is below ‘at risk’ / prediabetes zone…”)

In fact when I was trying back in 2019 it was two HbA1c results below 42, six months apart, without taking any diabetes medication.

I also came across the term 'Prolonged Remission' as being 5 years or more (see attached)

 

[saffron15]

I had first hba1c almost a year ago having moderated my diet a bit as told cholestral creeping up. 69 then four weeks later 64. I lost more than a stone before starting on metformin. I was put on an SGLT2 and statin in September. Hba1c 51.
Does the research mean I should concentrate on losing weight? I was 89kg when first diagnosed and would say I was a longterm fatty. I felt obliged to stop my low carb 100 to 120 when put on SGLT2. In December hba1c was 44. I was given choice in February to drop SGLT2 or one metformin. I chose latter as due an eye op. Do I need to drop SGLT2 and remaining metformin to be considered in remission? I'm in my seventies and was told SGLT2 was good for cardiovascular health so suspect it won't be dropped.
My weight now is 73 kg so about 19% drop. I'm still overweight so would want to loose more.

 

[Eddy Edson]

As a general point, I don't think there's any virtue or benefit in dropping meds if they are continuing to be useful. I know that SGLT2i's are supposed to have substantial cardiorenal benefits & in your position I'd probably want to stay on them regardless of HbA1c. For whatever that's worth!

Anyway, a downside of all this remission talk is that it risks making it seem like cutting meds is something always to be desired, which is just not true much of the time.

Similar for GLP and GIP meds, which have a growing body of evidence for cardiorenal, cancer, dementia benefits beyond weight loss and glucose control. If I were on one of these I'd probably want to stick with it, regardless of my "remission" status.

 

[grovesy]

Well I was advised to lose weight when I was diagnosed with impaired glucose tolerance (now known as prediabetes), back o

 

[Burylancs]

@Burylancs
Were you advised to lose weight when you were diagnosed? I wasn't in 2022, only to take Metformin.

I Certainly was way back in November 1992. I stuck to 1800 calories a day and dropped milk and butter/margerine entirely. Six months later the Consultant was over the Moon with my weight loss and 5.6% HbA1c. We called under 6% the '6% Club' in those days, the fallacious 'remission' was invented 20 years later after the 'reversal' baloney was abandoned. The original Consultant I had ( my GP said he didn't know much about Diabetes and just referred his patients to the local hospital Diabetes Centre) was a big fan of Weight Watchers and said they had 'got it right'.

 

[Burylancs]

Where do those figures come from?

The study says losing 1% of bodyweight had a 2.17 % probability of partial remission and a 2.74 probability of complete remission. Assuming 51% probability of remission is remission, 2.17 goes into 51 19 times i.e. 19% of bodyweight.

 

[Burylancs]

As a general point, I don't think there's any virtue or benefit in dropping meds if they are continuing to be useful. I know that SGLT2i's are supposed to have substantial cardiorenal benefits & in your position I'd probably want to stay on them regardless of HbA1c. For whatever that's worth!

Anyway, a downside of all this remission talk is that it risks making it seem like cutting meds is something always to be desired, which is just not true much of the time.

But included in the definition of this so-called 'remission' is that the T2 is not taking anti-hyperglycemic medication so anybody on metformin or gliclazide etc cannot claim to be in 'remission' whatever their HbA1c is. Obviously in espousing 'remission' so enthusiastically DiabetesUK, seemingly telling newbies the object of good control of T2 is not to take medication, is irresponsible one-size-fits-all stuff. DiabetesUK seems to be trying to impose an anti-vaxxer, anti-medication ideology on the T2 community.

 

[Martin.A]

As a general point, I don't think there's any virtue or benefit in dropping meds if they are continuing to be useful. I know that SGLT2i's are supposed to have substantial cardiorenal benefits & in your position I'd probably want to stay on them regardless of HbA1c. For whatever that's worth!

Anyway, a downside of all this remission talk is that it risks making it seem like cutting meds is something always to be desired, which is just not true much of the time.

Similar for GLP and GIP meds, which have a growing body of evidence for cardiorenal, cancer, dementia benefits beyond weight loss and glucose control. If I were on one of these I'd probably want to stick with it, regardless of my "remission" status.

I've always taken the position that I don't want to be taking any medication unless it's absolutely necessary. My late mother and late father-in-law started every day with a line-up of pills and I don't want that to be me if I can avoid it, although I'm sure there'll come a time when quality of life means I'll have no choice - I am 77, after all. Apart from antibiotics at various times I don't think I'd ever been prescribed anything until my T2 diagnosis, when I was put on Metformin.

 

[Burylancs]

.

Diabet

I've always taken the position that I don't want to be taking any medication unless it's absolutely necessary. My late mother and late father-in-law started every day with a line-up of pills and I don't want that to be me if I can avoid it, although I'm sure there'll come a time when quality of life means I'll have no choice - I am 77, after all. Apart from antibiotics at various times I don't think I'd ever been prescribed anything until my T2 diagnosis, when I was put on Metformin.

But how do you define 'absolutely necessary' ? Surely the fashionable medical trend now is preventive medicine, start well ahead of the threat as with Statins.

 

[JITR]

I certainly was [told to lose weight] way back in November 1992. I stuck to 1800 calories a day and dropped milk and butter/margerine entirely. Six months later the Consultant was over the Moon with my weight loss and 5.6% HbA1c. We called under 6% the '6% Club' in those days ... The original Consultant I had ( my GP said he didn't know much about Diabetes and just referred his patients to the local hospital Diabetes Centre) was a big fan of Weight Watchers and said they had 'got it right'.

That's it in a nutshell. Lose weight on any sensible diet that works for you.