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Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial

W. Timothy Garvey
May 1, 2020; 43:1085-1093
Emerging Therapies: Drugs and Regimens




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Time Course of Normalization of Functional {beta}-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes

OBJECTIVE

To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss.

RESEARCH DESIGN AND METHODS

A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA1c <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once.

RESULTS

During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480–811) pmol/min/m2 at baseline to 736 (542–998) pmol/min/m2 at 5 months, 942 (565–1,240) pmol/min/m2 at 12 months (P = 0.028 from baseline), and 936 (635–1,435) pmol/min/m2 at 24 months (P = 0.023 from baseline; n = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857–1,507] pmol/min/m2) by 12 (P = 0.064) and 24 (P = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4–67] to 107 [59–163] pmol/min/m2; P < 0.0001) and then remained stable at 12 and 24 months (110 [59–201] and 125 [65–166] pmol/min/m2, respectively; P < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226–429] pmol/min/m2; P < 0.0001).

CONCLUSIONS

A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.




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Scholarship applicants sought for 2020 Institute for Teaching and Learning

This year’s Institute for Teaching Learning program is scheduled for Aug. 23-26 in Atlanta. Now in its 14th year, with over 700 alumni, the program combines presentations, discussions, small group activities and peer-to-peer learnings to give participants new teaching skills. The onsite program is followed by a six-month distance learning experience that include online activities and interactive webinars.




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National Children’s Dental Health Month highlights optimally fluoridated water

This year the February observance of National Children’s Dental Health Month honors the 75th anniversary of community water fluoridation with its theme, “Fluoride in water prevents cavities! Get it from the tap!”




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Addressing caries through the lens of social justice, health equity, human rights

It’s a conviction that was published in the November issue of The Journal of the American Dental Association and the basis for the October 2019 forum that Dr. Francisco Ramos-Gomez fostered, where dentists, physicians, nurses and public health and public policy experts proposed, discussed and recommended solutions for preventing early childhood caries through the lens of social justice, health equity and human rights.




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Tampa Bay Lightning team dentist puts players’ mouths back together again

When Dr. Gil Rivera became a dentist, he had no idea his career would take him to the bloodied and bruised front lines of the NHL, but nearly 18 years later, he continues to treat the ravaged mouths of professional hockey players as the team dentist of the Tampa Bay Lightning.




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IADR, AADR cancel general session in light of coronavirus

The International Association for Dental Research and American Association for Dental Research have canceled their general session scheduled for March 18-21 in Washington, D.C., in light of the coronavirus disease outbreak.




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How dentists can keep the lights on during economic downturn

The ADA is streaming a free practice management webinar March 25 designed to help dentists predict short- and long-term impacts on their business operations during tough economic times and teach them how taking the right steps now can minimize their risk during the COVID-19 outbreak and its aftermath.




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JADA’s new CSA Corner highlights ACE Panel survey results on HPV vaccine

Dentists’ comfort levels and perceived roles in discussing and administering the human papillomavirus vaccine appear to vary, according to the results of an American Dental Association Clinical Evaluators Panel survey published in The Journal of the American Dental Association.




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Petrobras sells Chevron $350M Texas plant bought for $1.2B

Chevron bought a Houston refinery for $350 million from Petrobras that had cost the Brazilian state oil company over $1.2 billion little over a decade earlier.




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Cancer patients on Medicaid might not benefit from experimental treatments, study finds

Cancer patients on Medicaid or who don't have insurance benefit less from experimental treatments, even if they get into clinical trials, a study published Thursday by JAMA Network Open has found.




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U.S. rural areas soon might be on front lines in COVID-19 pandemic

The COVID-19 pandemic has left a path of destruction in urban centers throughout the northeastern United States, but the next outbreak hotspots could have even deadlier effects in rural areas.




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Combination of HIV, hepatitis C, MS drugs might resolve COVID-19 infection

Combination therapy with interferon beta-1b plus lopinavir-ritonavir and ribavirin appears to improve symptoms and shorten hospital stays for people with mild to moderate COVID-19.




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Social Innovation for Refugee Inclusion: From Bright Spots to System Change

In the three years since the European migration and refugee crisis vividly captured public attention, a wave of innovative initiatives has emerged to help newcomers settle into receiving societies. Now, as the sense of crisis abates, this report explores what these initiatives will need to do to outlast the hype and produce lasting change on key integration issues such as housing, economic inclusion, and community building.




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Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits

OBJECTIVE

We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study.

RESEARCH DESIGN AND METHODS

We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18–65 years, mean BMI >40 kg/m2, mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models.

RESULTS

During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m2.

CONCLUSIONS

Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.




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Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes

OBJECTIVE

To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone.

RESEARCH DESIGN AND METHODS

Forty-five patients with poorly controlled (HbA1c 7–11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA); 2) canagliflozin 100 mg/day (CANA); or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated.

RESULTS

The mean decrease from baseline to 16 weeks in HbA1c was –1.67 ± 0.29% (P = 0.0001), –0.89 ± 0.24% (P = 0.002), and –1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was –6.0 ± 0.8 kg (P < 0.0001), –3.5 ± 0.5 kg (P < 0.0001), and –1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked.

CONCLUSIONS

These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.




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Mars' magnetic field emerged earlier and lasted longer than previously thought

Mars' ancient magnetic field emerged earlier and persisted for longer than scientists previously thought, according to a new study.




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Astronomers find black hole just 1,000 light-years from Earth

Scientists have discovered the closest black hole to Earth, located just 1,000 light-years away.




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New map highlights China's export-driven CO2 emissions

China produces a whole lot of stuff -- stuff that gets bought by the rest of the world. In 2019, China exported approximately $2.5 trillion dollars worth of goods.




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On This Day, May 9: Freighter collapses Tampa Bay bridge, killing 35

On May 9, 1980, a Liberian freighter rammed a bridge in Florida's Tampa Bay, collapsing part of the span and dropping 35 people to their deaths.




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Rupert Grint, Georgia Groome confirm daughter's birth

Rupert Grint, who played Ron Weasley in the "Harry Potter" films, welcomed his first child, a daughter, with his girlfriend, Georgia Groome.




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[ Royalty ] Open Question : Why do males often name their male kids the same name, and a number, but females do not do the same for their daughters?

(I am in the USA). There was 8 Henry s https://en.wikipedia.org/wiki/Henry_VIII_of_England




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[ Singles & Dating ] Open Question : I miss my ex girlfriend's daughter what can I do ?

Hello I am a man 36 years old and, My ex girlfriend and I and I were together from January to August 2012, my ex girlfriend's daughter was very affectionate with me, I miss her what I can do I was very fond of her, what can I do ?




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[ Religion & Spirituality ] Open Question : Atheists, I always thought Roger Daltrey led the WHO, and not this Ted Ross guy. Who is he anyway? What instrument does he play?

What band was he with before?




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Eight Key U.S. Immigration Policy Issues: State of Play and Unanswered Questions

Amid a significant reshaping of immigration policy by the Trump administration, a range of immigration topics that have not been at the forefront of debate merit further information sharing with the public and policymakers. This report examines eight issues areas that are deserving of additional review and could form the basis for future action by Congress, including H-1B reform and treatment of unaccompanied minors.




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The Right Way to Talk across Divides

“Conversational receptiveness” can be learned

-- Read more on ScientificAmerican.com



  • Mind
  • Behavior & Society

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Iraq War Naysayers May Have Hindsight Bias

Antiwar liberals last week got to savor the four most satisfying words in the English language: "I told you so."




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Why Torture Keeps Pace With Enlightenment

In the year 65, the Roman emperor Nero discovered that a group of nobles had hatched a conspiracy to kill him. The tyrant captured the suspects one by one and threatened them with torture; most confessed and implicated others. One of the conspirators, Epicharis, was publicly tortured -- her bones...




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What Obama Might Learn From Emily Dickinson

Tell all the Truth but tell it slant/Success in Circuit lies/Too bright for our infirm Delight/The Truth's superb surprise . . .




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Deciding Which Road to Take: Insights into How Migrants and Refugees in Greece Plan Onward Movement

EU policy debates about moving asylum seekers from overburdened frontline countries, such as Greece and Italy, to other Member States rarely consider how migrants form and act on preferences for certain destinations—and how difficult it may be to change these views. This issue brief explores decision-making among migrants in Greece, including how living conditions, jobs, and legal status factor in.




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Silt Part 2 - Fighting the sea

On October 29th, 2012, Hurricane Sandy hit the tri-state area. I was lucky enough to be unaffected as I live on a hill in a central portion of Queens but I had two family members who lost power for a week. I also had co-workers who live in some of the most hard-hit areas of Brooklyn and Queens. Rereading Macfarlane's "Silt" chapter after Sandy was a sobering experience as I wondered what such a walk in parts of Queens or New Jersey would involve.

In the aftermath of Sandy, I've listened to radio interviews with Dutch engineers who have advocated sea gates and houses on stilts. I've read proposals about sea walls.  In the past week, Governor Cuomo has suggested a buyout of homes in areas likely to flooded again in the future. Once the state buys the land, the homes will be demolished and the land left empty. To quote Governor Cuomo, "there are some parcels that Mother Nature owns...She may only visit once every few years...but she owns the parcel and when she comes to visit, she visits."

However, people who live in flooded and devastated areas such as Freeport, Breezy Point or the Rockaways are reluctant to say goodbye to their communities and shore-based lifestyles. Mr. Cuomo accepts that man cannot ultimately defeat nature, which is why, for example, parts of the English coast are crumbling away without the UK spending billions on sea walls or sea gates (although London is protected by the Thames Barrier). Inhabitants of New York and New Jersey seem more willing to fight nature with man-made barriers, artificially-created natural shorelines, and architectural changes such as in the Netherlands. In the end, residents of NYC will have to decide how much money they wish to spend to protect and maintain their current lifestyles and residences.




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Thoughtful Investments Are Needed to Effectively Engage Volunteers in Refugee Integration

WASHINGTON — Rapid arrivals of humanitarian migrants in Europe and North America have been matched by an equally unprecedented outpouring of public support. As offers to volunteer and donate pour in, many have asked whether this generosity can be harnessed to ease pressures on overburdened receiving communities and service providers. But using volunteers to meet the longer-term integration needs of resettled refugees and recognized asylum seekers is not an automatic salve: it requires thoughtful training and investment to be effective.




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Naughty Day After "Faux Paella"

Nicky Riemer from Union Dining is one of 20 of Victoria's top chefs who will unite to raise funds for vulnerable children at Gastronomique on November 25. The gala food and wine charity evening will support Anglicare Victoria. Now in its 12th year, Gastronomique includes signature dishes, fine wine and entertainment. www.gastronomique.org.au




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Jerusalem artichokes cooked overnight with hazelnut praline

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, shared by Dan Hunter, chef and owner of Otways' restaurant Brae.




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Microvascular and Cardiovascular Outcomes According to Renal Function in Patients Treated With Once-Weekly Exenatide: Insights From the EXSCEL Trial

OBJECTIVE

To evaluate the impact of once-weekly exenatide (EQW) on microvascular and cardiovascular (CV) outcomes by baseline renal function in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

RESEARCH DESIGN AND METHODS

Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria).

RESULTS

EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m2 [95% CI –0.27 to 0.70]). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio [HR] 0.87 [95% CI 0.70–1.07]). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 [95% CI 0.74–0.98]). Retinopathy rates did not differ by treatment group or in the HbA1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR <60 mL/min/1.73 m2 did not differ by group. Those with eGFR ≥60 mL/min/1.73 m2 had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 [95% CI 0.58–0.93]; P for interaction = 0.035) and CV death (HR 1.08 [95% CI 0.85–1.38]; P for interaction = 0.031).

CONCLUSIONS

EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m2 in analyses unadjusted for multiplicity.




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Confirming the Bidirectional Nature of the Association Between Severe Hypoglycemic and Cardiovascular Events in Type 2 Diabetes: Insights From EXSCEL

OBJECTIVE

We sought to confirm a bidirectional association between severe hypoglycemic events (SHEs) and cardiovascular (CV) event risk and to characterize individuals at dual risk.

RESEARCH DESIGN AND METHODS

In a post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering (EXSCEL) participants, we examined time-dependent associations between SHEs and subsequent major adverse cardiac events (CV death, nonfatal myocardial infarction [MI] or stroke), fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for acute coronary syndrome (hACS), hospitalization for heart failure (hHF), and all-cause mortality (ACM), as well as time-dependent associations between nonfatal CV events and subsequent SHEs.

RESULTS

SHEs were uncommon and not associated with once-weekly exenatide therapy (hazard ratio 1.13 [95% CI 0.94–1.36], P = 0.179). In fully adjusted models, SHEs were associated with an increased risk of subsequent ACM (1.83 [1.38–2.42], P < 0.001), CV death (1.60 [1.11–2.30], P = 0.012), and hHF (2.09 [1.37–3.17], P = 0.001), while nonfatal MI (2.02 [1.35–3.01], P = 0.001), nonfatal stroke (2.30 [1.25–4.23], P = 0.007), hACS (2.00 [1.39–2.90], P < 0.001), and hHF (3.24 [1.98–5.30], P < 0.001) were all associated with a subsequent increased risk of SHEs. The elevated bidirectional time-dependent hazards linking SHEs and a composite of all CV events were approximately constant over time, with those individuals at dual risk showing higher comorbidity scores compared with those without.

CONCLUSIONS

These findings, showing greater risk of SHEs after CV events as well as greater risk of CV events after SHEs, validate a bidirectional relationship between CV events and SHEs in patients with high comorbidity scores.




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Declutter Your Inbox. Subscribe to Email Newsletters Straight Into Inoreader

You have mail! Inoreader now allows you to subscribe to Email Newsletters just as regular RSS feeds. By creating a…




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Inoreader mobile apps updated to support Automatic Night Mode, Microblogs, Sort by Magic and popularity indicators.

Hey, it’s been quite some time without updates on this front, but our latest updates to our Android and iOS…




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Thinking with AND: Insights from KIND’s story

“I’m a confused Mexican Jew.” So says Daniel Lubetzky, Founder and CEO of KIND Snack, in his very personal interview with Columbia faculty member David Rogers at BRITE ’16. Their discussion touched on the many ideas behind KIND Snacks, from the beginnings of the company, to the strategic thinking that forces Lubetzky to stay away […]




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The Breakfast That Boosts Weight Loss By 65%

The food lowers cravings for high-sugar and high-fat foods and suppresses appetite during the day.

Support PsyBlog for just $5 per month. Enables access to articles marked (M) and removes ads.

→ Explore PsyBlog's ebooks, all written by Dr Jeremy Dean:




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Online Therapy: A Powerful Tool in the Fight Against Covid 19

The coronavirus pandemic is affecting billions of people around the world today. Coronavirus, now called covid 19, is a type of virus that is usually found in animals and is rarely transmitted to humans. According to reports from the World Health Organization, covid 19 likely originated from a seafood and meat market in Wuhan, China, […]




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does resurge work : Resurge weight reduction supplement is a...



does resurge work : Resurge weight reduction supplement is a distinct advantage program that would bolster your ascent to control. It will change you and make you more grounded than at any other time with improved wellbeing that can assist you with getting away from heftiness. This Resurge audit tells how the Supplement will help your lack of sleep and weight reduction cause. Improved digestion change will enable the body to acquire vitality.




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Five Things Science Has Taught Us About Asexuality

Research has found that around 1% of the population is asexual, a term usually defined as either a lack of sexual attraction or a lack of desire for partnered sexual activity [1]. Asexuality is something that many people are not familiar with and, as a result, there are lots of myths and misconceptions about it. So, let’s take a moment to review some key facts about asexuality that science has taught us.




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People Who Have Lost Their Religion Show “Residues” Of Religious Past In Their Thoughts And Behaviours, Study Claims

By Emma Young. Formerly religious are more prosocial than those who were never religious, researchers argue.




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Massachusetts Gets Green Light to Pilot Innovative Science Assessment

Massachusetts is the fifth state to join the Innovative Assessment Demonstration Authority created through the Every Student Succeeds Act, which allows states to experiment with new forms of testing.




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Utah Ruling Highlights Sticky Issue of Partisan School Board Elections

In Florida, Indiana, Kansas, North Carolina, Tennessee and Utah, Republicans are arguing that candidates for local and state school boards should run on party tickets.




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Betsy DeVos Greenlights ESSA Plans for Nebraska and North Carolina

U.S. Ed Secretary DeVos has approved plans for 46 states, plus the District of Columbia and Puerto Rico. Still waiting: California, Florida, Oklahoma, and Utah.




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'A Game Changer': Virginia Teachers Close to Getting Collective Bargaining Rights

A measure now before Virginia's governor would let teachers bargain with local boards over wages and working conditions if a local board authorizes it.




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Election Night Brings Highs and Lows for Oklahoma Teachers

About a dozen teachers running for state legislative seats gathered with their supporters in Tulsa for a watch party on election night. The results were better for some than others.




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I Was an Angry Teacher Fighting for Better Education Policy. Now, I'm Shaping It

What goes on behind all the closed doors in politics? Most teachers never get a chance to find out, writes teacher-turned-politician John Waldron.